Format 2016: how to get asthma control: from PubMed to the tricks of the trade

How to get Asthma Control: from PubMed to the Tricks of the Trade

Attilio BonerUniversity ofVerona, Italy

[email protected]

IntroductionEstablishment of a partnershipThe problem of adherenceEffective use of devicesWritten action plansEffective use of controller medicationsEffective use of quick-relief medicationsEnvironment controlOxidative stress reduction and dietAddressing co-morbidities Monitoring the child asthmaSummary and Conclusions

Asthma Control General Considerations

Guidelines for asthma management have evolved considerably during the last decade, from treatment recommendations based on the level of asthma severity to the current emphasis on achieving full asthma control. •National Asthma Education and Prevention Program Coordinating Committee. Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. 2008. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm Date last accessed: December 18, 2012. Date last updated: 2008. •British Thoracic Society Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma: a national clinical guideline. Thorax 2009;63(Suppl. 4):i1–21.

Asthma control is defined as the extent to which the various manifestations of asthma are reduced or removed by treatment.•Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/ European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59–99.

An official American Thoracic Society/ European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for

clinical asthma trials and clinical practice. Reddel HK, Am J Respir Crit Care Med 2009;180:59–99.

Asthma control includes

2 components:

1. The level of clinical asthma control, which is gauged from features such as symptoms and the extent to which the patient can carry out activities of daily living and achieve optimum quality of life, and

2. The risk of future adverse events including loss of control, exacerbations, accelerated decline in lung function,

and side-effects of treatment.

PRESENT

FUTURE

refers to the difficulty in controlling asthma with treatment (i.e. the activity of the underlying disease state)

Asthma Severity and Control

Asthma severity and control are related but not interchangeable

concepts

Asthma control refers to the extent to which asthma symptoms or associated features are alleviated by treatment

asthma severity

Reddel HK, Am J Respir Crit Care Med 2009;180:59–99.Taylor DR, Eur Respir J 2008;32:545–554.

Bronchial biopsy specimens before and after repeated inhaled methacoline

challenge.Panels A and C respiratory epithelium before the challenges.

Biopsy specimens immunostained with an antibody to collegen type III(in Panels A and B).

Panels B and Drespiratory epithelium 4 days after the challenges.

Biopsy specimens stained with peridic acid-Shiff to detect goblet cells (in Panels C and D).

Effect of bronchoconstriction on airway remodeling

in asthma. Grainge CL. N Engl J Med. 2011;364(21):2006-15

Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations.Matsunaga K, J Allergy Clin Immunol Pract. 2015;3(5):759-764.

annual rate of decline in post-bronchodilator FEV1 (mL/year)

-10 –

-10 –

-20 –

-30 –

-40 –

-50 –

-60 -

exacerbation numbers

0 1 ≥2

-13.6 mL/year

-41.3 mL/year

-58.3 mL/year

P < 0.01

P < 0.0001

128 patients with asthma3-year follow-up

Trajectories of lung function during childhood.Belgrave DC, Custovic A. Am J Respir Crit Care Med.

2014;189:1101-9. birth cohort,

specific airway resistance (sRaw) at age 3 (n = 560), 5 (n = 829), 8 (n = 786), and 11 years (n = 644).

wheeze phenotypes (no wheezing, transient, late-onset, and persistent)

atopy phenotypes (no atopy, dust mite, non-dust mite, multiple early, and multiple late).

wheezers who experienced exacerbation

had significantly poorer lung function

(higher sRaw) than children who never wheezed.

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease.

Lange P, N Engl J Med. 2015;373(2):111-22.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline FEV1 over time.

Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms.

Of the 332 persons with COPD at the end of the observation

period60 –

50 –

40 –

30 –

20 –

10 –

0

48%52%

FEV1 before 40 years of age

≥80%

and had a rapid

decline in FEV1

thereafter, of 53±21 ml

per year*<80%

low FEV1 in early

adulthood and a

subsequent mean decline

in FEV1 of 27±18 ml per year*

*P<0.001 for the decline

participants in 3 independent cohorts stratified according to lung function [FEV1 ≥80% (n=2207) or <80% (n=657) of the predicted value) at cohort inception (mean age of patients, approximately 40 years] and the presence or absence of COPD at the last study visit.

we then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end.

Follow-up: 22 years.

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease.

Lange P, N Engl J Med. 2015;373(2):111-22.

82 children (6-11 years) and 725 adolescent/adult patients ≥12 years (TENOR study).

Follow-up: 24 months.

in Children with Consistently Very Poorly

Controlled Asthma OR for

6.4

HOSPITALIZATION, ED VISIT, or

CORTICOSTEROID BURST

7 –6 –5 –4 –3 –2 –1 –0

Consistently very poorly controlled asthma increases risk for future severe asthma

exacerbations.Haselkorn T, J Allergy Clin Immunol. 2009;124(5):895-902.

The Poorly Explored Impact of Uncontrolled Asthma

O’Byrne, CHEST 2013;143:511 Poorly controlled asthma adversely affects

children’s cardiovascular fitness, while children with well-controlled asthma perform at the same level as their peers.

Children with uncontrolled asthma also have a higher frequency of obesity than children with controlled asthma.

Children with poorly controlled asthma are more likely to have learning disabilities compared with those with good control.

The Poorly Explored Impact of Uncontrolled Asthma

O’Byrne, CHEST 2013;143:511 Adults patients with asthma are at

greater risk for depression. Poorly controlled asthma increases the risks of

severe asthma exacerbations following upper respiratory and pneumococcal pulmonary infections.

Lastly, the risks of uncontrolled asthma during pregnancy are substantially greater than the risks of recommended asthma medications.

Treatments to maintain asthma control are the best approach to optimize maternal and fetal health in the pregnancies of women with asthma.

The aim of treatment of asthma is:

1) to control symptoms, 2) to restore full physical and psychosocial functioning, 3) to eliminate interference with social relationships and

quality of life.

The goals of asthma treatment

To reach these goals, people with asthma

(including children and their parents) must at least:

1) be able to use prescribed drugs in the proper manner to prevent or control symptoms,

2) identify and avoid the triggers that cause symptoms, 3) develop or maintain family and other necessary social

support,4) communicate effectively with healthcare providers.

The aim of treatment of asthma is:

1) to control symptoms, 2) to restore full physical and psychosocial functioning, 3) to eliminate interference with social relationships and

quality of life.

The goals of asthma treatment

To reach these goals, people with asthma

(including children and their parents) must at least:

1) be able to use prescribed drugs in the proper manner to prevent or control symptoms,

2) identify and avoid the triggers that cause symptoms, 3) develop or maintain family and other necessary social

support,4) communicate effectively with healthcare providers.

The failure to see management by patients as a behavioural

process based largely on an individual's ability to self

regulate may lead to inefective asthma control despite optimal

therapy prescription


[email protected]



Management of chronic disease by practitioners and patients: are we teaching the wrong things?

Clark NM, BMJ 2000;320:572-5.

The patient should be the primary manager of chronic disease, guided and coached by a doctor or other practitioner to devise the best therapeutic regimen.

The practitioner and patient should work as partners, developing strategies that give the patient the best chance:

1) to control his or her own disease and 2) to reduce the physical, psychological, social, and

economic consequences of chronic illness.

patient

Bandura’s Social Cognitive Theory:Determinants of Improved Self Regulation

Mastery experiences (practice opportunities)

Social modeling (watching others succeed)

Social persuasion (from a trusted source)

Psychological response (decreased stress)

+ + =

Self Regulation

Self regulation is the process of:

It is a means by which patients determine what they will do, given:

1) observing, 2) making judgments (evaluations), and 3) reacting realistically and appropriately to one's

own efforts to manage a task.

1) their specific goals, 2) social context, and 3) their perceptions of their own capability.

Clark NM, BMJ. 2000;320:572-5

the patient

Self Regulation

Self regulation is the process of:

It is a means by which patients determine what they will do, given:

For example, a child with asthma who wants to play football

1) their specific goals, 2) social context, and 3) their perceptions of their own capability.

i. thinks drugs will help and so uses them preventively,

ii. takes a reliever drug when exercising strenuously,

iii. seeks moral support from his friends and coaches,

iv. uses other strategies that enable him to reach his personal goal.

v. he learns which strategies are effective through

self regulation.

Clark NM, BMJ. 2000;320:572-5

1) observing, 2) making judgments (evaluations), and 3) reacting realistically and appropriately to one's

own efforts to manage a task.

Motivational interviewing derives from Prochaska and DiClemente’s transtheoretical model of change.This model explains behavioral change as a process in which individuals pass through 5 stages:

1) precontemplation,

2) contemplation,

3) preparation,

4) action,

5) maintenance.

Transtheoretical therapy: toward a more integrative model of change.

Prochaska, JO. Psychotherapy: Theory, Research & Practice, 1982;19:276

Motivational interviewing offers an alternative response to ambivalence.

struggles with ambivalence as a normal part of the process of change and that

patient motivation and readiness to change are not static traits, but rather dynamic states that can be greatly influenced by interactions between provider and patient.

NORMAL

OVERCOMING AMBIVALENCE

PRINCIPLES OF MOTIVATIONAL INTERVIEWING: creating the conditions for change

• Express empathy.

• Avoid argument.

• Develop a discrepancy.

• Roll with resistance.

• Support self-efficacy.

Non-smoking twin

Twin who smokes 3

cigarettes per day

http://bp0.blogger.com/_hBmzKAUGw88/R0sf_Q22o4I/AAAAAAAAAEQ/_c6n7CBd2xI/s1600-h/untitled.bmp

“the change only depends on

me”).

“I have absolutely no influence on

asthma change,”

Higher risk of poor control

Asthma patients' perception of their ability to influence disease control and management

Laforest L, Ann Allergy Asthma Immunol 2009;102:378

Internal locus of control

OR = 2.68

There are 2 types of patient needs to be addressedduring the medical interview:

Physicians’ communication and parents’ evaluation of pediatric consultations. Street RL.

Med Care. 1991;29:1146

cognitive (serving the need to know and understand) and

affective (serving the emotional need to feel known and understood).“understand” “be understood”

Active listening is a specific communication skill which involves:

- giving free and undivided attention to the speaker,

- placing all of one’s attention and awareness at the disposal of another person,

- listening with interest and appreciating without interrupting

- concentrating on everything the person is conveying, both verbally and nonverbally (body language).

Active listening More than just paying attention Robertson, Aust Fam Physicians 2005;34:1053

in

out

Active listening is a specific communication skill which involves:

- giving free and undivided attention to the speaker,

- placing all of one’s attention and awareness at the disposal of another person,

- listening with interest and appreciating without interrupting

- concentrating on everything the person is conveying, both verbally and nonverbally (body language).

This is a rare and valuable commitment,

as most discussions involve competition for a space

to speak.

Active listening More than just paying attention Robertson, Aust Fam Physicians 2005;34:1053

in

out

emotions play a part in the process of medical care in 3 interrelated ways:

EMOTIONS AND THE MEDICAL CARE PROCESS

First, both physicians and patients have emotions.

Second, both physicians and patients show emotions,

Third, both physicians and patients judge each other’s emotions.

Nonverbal Sensitivity of Physicians

element nonverbal index: -facial expressivity

-frequency of smiling;

-eye contact and nodding,

-body lean

-body posture

-tone of voice

It seems likely that physicians’ nonverbal

behavior

significantly influences patients’

likelihood of deciding for or against recommended

treatment options.

Three elements of communication – and the "7%-38%-55% Rule“

Mehrabian (1971) Silent messages. Wadsworth, Belmont, California.

•there are basically three elements in any face-to-face communication:1) words, 2) tone of voice and 3) body language. These three elements account differently for the meaning of the message:

- Words account for 7%- Tone of voice accounts for 38% and- Body language accounts for 55% of the message.

2

Enabling Effective Child Participation

Parents and children themselves are more satisfied and

adherence to the

treatment regimen is enhanced.

when the child is addressed in information

gathering and in the creation of the treatment

plan.

Children 7 years and older are:

1)more accurate than their parents in providing health data that predicts future health outcomes, although

2) they are worse at providing past medical histories.

Enabling Effective Child Participation

Children's contributions to pediatric outpatient encounters. van Dulmen AM. Pediatrics. 1998;102:563-8

21 consulting pediatricians

videotaped a total of 302 consecutive outpatient encounters.

Children's contributions to the outpatient encounters

5 –

4 –

3 –

2 –

1 –

0

4%only

Children's contributions to pediatric outpatient encounters. van Dulmen AM. Pediatrics. 1998;102:563-8

21 consulting pediatricians

videotaped a total of 302 consecutive outpatient encounters.

Children's contributions to the outpatient encounters

5 –

4 –

3 –

2 –

1 –

0

4%only

Always talk with

the child !

Adolescents’ Roles in Health Care Communication and

Decisional Authority Leveton Pediatrics 2008;121:e1441Adolescents must receive

understandable information:

1) to enable an understanding of the condition,

2) what to expect with various tests and treatments,

3) the range of acceptable and practical alternative care plans,

4) likely outcomes of each option.

The tolerant model of decision making

1) addresses potentially harmful decisions by giving weight to the adolescent’s decision,

2) with the proxy taking the role of:- educator, - discussant,- challenger, and- shared decision maker.


Decisional Authority Leveton Pediatrics 2008;121:e1441

The tolerant model of decision making

1) addresses potentially harmful decisions by giving weight to the adolescent’s decision,

2) with the proxy taking the role of:- educator, - discussant,- challenger, and- shared decision maker.


Decisional Authority Leveton Pediatrics 2008;121:e1441

the adolescent’s

decision should not

be overrided but

discussed.

X

X

Oral communication strategies for health care providersTable II

Health literacy and asthma Rosas-Salazar C, JACI 2012;129:935-42

10 out of 100 instead of 10%

Oral communication strategies for health care providersTable II

Health literacy and asthma Rosas-Salazar C, JACI 2012;129:935-42

10 out of 100 instead of 10%

Learning from tragedies: clinical lessons from the Climbié report.

Marcovitch H. Qual Saf Health Care 2003 ;12:82–3.

“doctors [should be taught] how to

write [so] that readers willunderstand” Trick of the Trade

from Lord Laming “UK

Secretary of State for Health”

who has carried out child protection review


[email protected]



•The term adherence is often used interchangeably with compliance and is preferred by some as it acknowledges the patient’s role as a partner in the decision-making process.Tilson HH. Adherence or compliance? Changes in terminology. Ann Pharmacother 2004; 38: 161-2

•Adherence is defined as “the extent to which a person’s behaviour – taking medication, following a diet, and/or executing lifestyle changes –corresponds with agreed recommendations from a healthcare provider.World Health Organization. Adherence to long-term therapies: evidence for action [online]. Available from URL: http://www.emro.who.int/ncd/Publications/adherence_report.pdf

Haynes R, Taylor D, Sackett D. Compliance in health care. Baltimore: The Johns Hopkins University Press, 1979.

Definition

http://www.emro.who.int/ncd/Publications/adherence_report.pdf

http://www.emro.who.int/ncd/Publications/adherence_report.pdf

non-adherence can be

as high as 32–56%Robinson DS, Eur Respir J 2003; 22: 478–483. Heaney LG, Thorax 2003; 58: 561–566.Gamble J, Respir Med 2011; 105: 1308–1315.

Poor inhaler technique is also common and should be addressed

Bracken M, Arch Dis Child 2009; 94: 780–

784. .

If non-adherence is present, clinicians should empower patients to make informed choices about their

medicines and develop individualised interventions to manage non-adherence.

Gamble J, Respir Med 2011; 105: 1308–1315.

Non-adherence to treatment should be

considered in all difficult-to-control patients

Non-Adherence to Treatment

Adherence to therapy

Bush A, Eur Respir Mon 2011;51:59-81

Doctors are notoriously poor at predicting which patients take treatment, and parents frequently overestimate adherence.

Useful tools include:

1) measurement of serum medication levels (prednisolone and theophylline);

2) obtaining a list of prescriptions supplied (collecting a prescription does not guarantee adherence, but failure to collect guarantees

non-adherence); Warner JO. BMJ 1995;311:663–666.

3) assessment of whether there is a supply of easily accessible in-date medication in the home.



Other adherence issues to be addressed include:

4) whether the child is supervised (often quite young children are left unsupervised by the carers); Orrell-Valente JK, Pediatrics 2008;122:e1186–e1192.

5) whether the child and family have an age-appropriate drug delivery device that is being used properly.

Repeated education in the use of medication devices is frequently required. Kamps AW, Pediatr Pulmonol 2000;29:39–42.

“It is, of course, one thing to identify poor adherence and quite another to address it.”



Other adherence issues to be addressed include:

4) whether the child is supervised (often quite young children are left unsupervised by the carers); Orrell-Valente JK, Pediatrics 2008;122:e1186–e1192.

5) whether the child and family have an age-appropriate drug delivery device that is being used properly.

Repeated education in the use of medication devices is frequently required. Kamps AW, Pediatr Pulmonol 2000;29:39–42.

“It is, of course, one thing to identify poor adherence and quite another to address it.”

!

Adherence estimated from electronic prescription and pharmacy fill records.

Patients were considered to be adherent if ICS use was ≥ 80% of prescribed.

Health Locus of Control scale was used to assess five sources (God, doctors, other people, chance, and internal).

OR for medication adherence in patients’ who had a stronger

belief that God determined asthma control 1.0 –

0.5 –

0.0

0.680.89

African American

White

Asthma medication adherence: the role of God and other health locus of control factors.

Ahmedani BK, Ann Allergy Asthma Immunol. 2013;110(2):75-9.

Parents accompanying 150 children aged 3–9 years with asthma attending asthma clinics.

OR FOR SOUTH ASIAN PARENTS COMPARED TO WHITE

0.30

3.19

TO GIVE PREVENTER

S DRUGTO CONSIDERES

DRUG MORE HARM THAN

GOOD

3.50 –

3.00 –

2.50 –

2.00 –

1.50 –

1.00 –

0.50 –

0

Parental attitudes towards the management of asthma in ethnic minorities.Smeeton NC, Arch Dis Child.

2007;92:1082-7.

351 children with asthma.

Parents of study participants completed the Asthma Numeracy Questionnaire.

Low parental numeracy

(1 cp 25 mg = 5 cp 5 mg)

OR for visits to the ED or urgent care for

asthma

1.772.0 –

1.5 –

1.0 –

0.5 –

0.0

p=0.04

Parental Numeracy and Asthma Exacerbations in Puerto Rican Children Rosas-Salazar C.

Chest 2013;144:92-8


Parents of study participants completed the Asthma Numeracy Questionnaire.

OR for visits to the ED or urgent care for

asthma

1.772.0 –

1.5 –

1.0 –

0.5 –

0.0

p=0.04

Parental Numeracy and Asthma Exacerbations in Puerto Rican Children Rosas-Salazar C.

Chest 2013;144:92-8

Trick of the trade:“speak as you eat”

Low parental numeracy

(1 cp 25 mg = 5 cp 5 mg)

ADHERENCE TO ALLERGEN AVOIDANCE ADVICE

%PATIENTS

USING

COVER

MATTRESS

40 -

30 -

20 -

10 -

0

17 %

39 %

0 %Without formal

education programEggleston

ARRD 1992;145:213

With usual clinic based education

effortKorsgaard

ARRD 1982;125:80

With a computer education program

Huss JACI 1992;89:836

Adherence with Inhaled Corticosteroids

typically ranging from 30% to 70%,

but on average lower than

50%1) Rand CS. Adherence to asthma therapy in the preschool child. Allergy. 2002;57 Suppl 74:48–57.

2) Jentzsch NS, Camargos PA, Colosimo EA, Bousquet J. Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods. Allergy. 2009 Oct;64(10):1458–62

3) Bender BG, Bender SE. Patient-identified barriers to asthma treatment adherence: responses to interviews, focus groups, and questionnaires. Immunol Allergy Clin North Am. 2005;25(1):107–30.

4) Milgrom H, Bender B, Ackerson L, Bowry P, Smith B, Rand C. Noncompliance and treatment failure in children with asthma. J Allergy Clin Immunol. 1996;98(6 Pt 1):1051–7.

These rates may even be an overestimate of true adherence in the general population, as study participants are likely to increase

their medication use as a manifestation of knowing they are being observed

(the Hawthorne effect)

Desai M, Curr Allergy Asthma Rep 2011;11:454

Studies assessing adherence to ICS in children and adolescents consistently demonstrate poor rates of adherence.









their medication use as a manifestation of

knowing they are being observed




compliance is significantly

less of an issue for ‘as required

therapy’ with β-agonists, compared

with regular therapy with

corticosteroids.









their medication use as a manifestation of

knowing they are being observed




If β2-agonists frequently very

likely the child is not taking ICS or he has a poor technique !

Background: A validated tool to assess adherence with inhaled corticosteroids (ICS) could help physicians and researchers determine whether poor asthma control is due to poor adherence or severe intrinsic asthma.Objective: To assess the performance of the Medication Adherence Report Scale for Asthma (MARS-A), a 10-item, self-reported measure of adherence with ICS.

Permission to use it should be obtained by requests to

[email protected]. Score: Alaways =1, Often=2, Sometimes=3, Rarely=4,

Never=5

Assessing the validity of self-reported medication adherence among inner-city asthmatic adults:

the Medication Adherence Report Scale for Asthma

CohenJL. Ann Allergy Asthma Immunol 2009;103:325-31

ICS

Self-reported Medication Adherence How often do you do the

following:1) Alaways2) Often3) Sometimes4) Rarely5) Never

High self-reported adherence was

defined as a mean MARS score of ≥4.5




Self-reported Medication Adherence How often do you do the

following:1) Alaways2) Often3) Sometimes4) Rarely5) Never

High self-reported adherence was

defined as a mean MARS score of ≥4.5

Ask the patients to tell you the name of the drugs.

Ask the patients to bring their drugs and the spacer at each visit.




Poor or non-adherence to treatment

Adolescents are at risk

reduced adherence to treatment smoking,

illicit drug use

a higher risk of fatal episodes

of childhood asthma.

are common

risk taking behaviours

ERS/ATS Guidelines, ERJ 2014;43:343-373

X

X

Hedlin G, E. RJ 2010;36:196-201

Psychological risk factors are prominent in children and young adults who subsequently die of asthma. Strunk RC, JAMA 1985;254:1193–1198.Bergström SE, Respir Med 2008;102:1335–1341. Similarly, in near-fatal asthma episodes in children, the children also showed significant denial, psychosocial pathology and delay in seeking treatment. Martin AJ, Pediatr Pulmonol 1995;20:1–8.

lack of concordance with prescribed medication due to psychosocial factors in chaotic

families,influence asthma control.

Non-Adherence: Psychosocial Issues

Most well trained professionals adopt a practical tactic that

processes through an ongoing assessment

and negotiation of the various components of the treatment.

A contractual approach to improving adherence Michaud Arch Dis Child 2004;89:943

There are clues for improvingadherence in general and the

adherence of adolescents with a chronic disorder such as asthma,

Most well trained professionals adopt a practical tactic that

processes through an ongoing assessment

and negotiation of the various components of the treatment.

A contractual approach to improving adherence Michaud Arch Dis Child 2004;89:943

There are clues for improvingadherence in general and the

adherence of adolescents with a chronic disorder such as asthma,

tricks of the trade:

1) “I have done the same thing when I was young so I do understand you …

and I like you but I cannot

agree”.

2) “If you have questions

or doubts this is my phone

number”.

OR for uncontrolled asthma

Low maternal education

Parental concerns about potential

adverse consequences of

medication

2.0 –

1.5 –

1.0 –

0.5 –

0

1.6 1.6

Uncontrolled asthma at age 8: The importance of parental perception towards medicationKoster ES. Pediatr Allergy Immunol 2011;22:462-8

Uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study.

Uncontrolled asthma defined as: ≥3 items present in the past month:

1) day-time asthma symptoms, 2) night-time asthma symptoms, 3) limitations in activities, 4) rescue medication use, 5) FEV1 < 80% predicted and 6) unscheduled physician visits because of asthma.

OR for uncontrolled asthma

Low maternal education

Parental concerns about potential

adverse consequences of

medication

2.0 –

1.5 –

1.0 –

0.5 –

0

1.6 1.6

Uncontrolled asthma at age 8: The importance of parental perception towards medicationKoster ES. Pediatr Allergy Immunol 2011;22:462-8

Uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study.

Uncontrolled asthma defined as: ≥3 items present in the past month:

1) day-time asthma symptoms, 2) night-time asthma symptoms, 3) limitations in activities, 4) rescue medication use, 5) FEV1 < 80% predicted and 6) unscheduled physician visits because of asthma.

Talk also about

treatment side-efffects

The Madison Avenue effect: How drug presentation style influences adherence and

outcome in patientswith asthma Clerisme-Beaty EM. JACI 2011;127:406-11

99 participants.Randomized to placebo

or montelukast in conjunction with a presentation mode that was either neutral or designed to increase outcome expectancy.

Adherence monitored electronically over 4 weeks.

4.0

OR for good adherence (≥80% prescribed doses)

4.0 -

3.0 –

2.0 –

1.0 –

0.00Presentation mode

designed to increase outcome expectancy

99 participants.Randomized to placebo

or montelukast in conjunction with a presentation mode that was either neutral or designed to increase outcome expectancy.

Adherence monitored electronically over 4 weeks.

4.0

OR for good adherence (≥80% prescribed doses)

4.0 -

3.0 –

2.0 –

1.0 –

0.00Presentation mode

designed to increase outcome expectancy

The use of an enhanced presentation aimed

at increasing outcome expectancy may lead to

improved medication adherence.

The Madison Avenue effect: How drug presentation style influences adherence and

outcome in patientswith asthma Clerisme-Beaty EM. JACI 2011;127:406-11


[email protected]

IntroductionEstablishment of a partnershipThe problem of adherenceEffective use of devicesWritten action plansEffective use of controller medicationsEffective use of quick-relief medicationsEffective control of inflammationOxidative stress reduction and dietAddressing co-morbidities Monitoring the child asthmaSummary and Conclusions


Role of inhaler competence and contrivance in‘‘difficult asthma’’

Mark L. Everard, Paediatric Respiratory Reviews 2003;4:135–142

Failure to deliver drug effectively to the lungs is the most common cause of referrals with ‘‘uncontrolled asthma’’.

This may be due to:

1) poor regime Compliance

or

2) poor device Compliance lack of Competence (the inability to use a device effectively) and/or Contrivance (knowing how to use a device effectively but choosing to use it in a non-effective way ).

the healthcare professional must be aware of the:

1) principles underlying aerosol delivery

2) aspects of patient behaviour.

more difficult

to address.

Role of inhaler competence and contrivance in‘‘difficult asthma’’

Mark L. Everard, Paediatric Respiratory Reviews 2003;4:135–142

Failure to deliver drug effectively to the lungs is the most common cause of referrals with ‘‘uncontrolled asthma’’.

This may be due to:

1) poor regime Compliance

or

2) poor device Compliance lack of Competence (the inability to use a device effectively) and/or Contrivance (knowing how to use a device effectively but choosing to use it in a non-effective way ).

the healthcare professional must be aware of the:

1) principles underlying aerosol delivery

2) aspects of patient behaviour.

more difficult

to address. ‘‘spacer disuse’’, omitting to use the spacerbecause it is inconvenient, is one of the most common forms of contrivance.

X

Contrivance with holding chamber-Spacer

100prescribed 65–73%

will use

Studies in children and adults suggest that 65–73% of patients prescribed an HC for use when administering regularly use their pMDI alone. Everard ML. Thorax 2000;55:811–814. Shim C. Am J Respir Crit Care Med 2000;161:A320

Contrivance with holding chamber-Spacer

100prescribed >85%

will use

Studies in children and adults suggest that 65–73% of patients prescribed an HC for use when administering regularly use their pMDI alone. Everard ML. Thorax 2000;55:811–814. Shim C. Am J Respir Crit Care Med 2000;161:A320

‘‘spacer disuse’’ had fallen to <15% suggesting that

addressing the issue in clinic can have a major impact on this potential reason for therapeutic

failure.Everard ML,

Ped Respir Rev 2003;4:135

Physician knowledge in the use of canister nebulizers. Kelling JS,. Chest . 1983;83:612-614 .

55 house officers and non-pulmonary attending staff from the Department of Medicine were interviewed individually.

Each physician was handed a placebo canister and asked a series of standard questions regarding the recognition, assembly, and correct inhalation technique of the device.

% participants correctly performing more than 4 of the 7 steps felt to constitute a correct

inhalation maneuver.

50 –

40 –

30 –

20 –

10 –

0

40%only!

% patient with difficulty in

Problems patients have using pressurized aerosol inhalers

Crompton GK. Eur J Respir Dis Suppl 1982;119:101 -6

51%

Co-ordinating aerosol

release with inspiration

Release of aerosol into the mouth caused a

halt of inspiration

60 –

50 –

40 –

30 –

20 –

10 –

0

12%

24%

Inspiration was achieved

through the nose with no air being drawn in

through the mouth

Use of pressurized aerosol inhalers

1173 out-patients

X

Freoneffect

Nasal inhalation as a cause of inefficient pulmonal aerosol inhalation technique in

children Pedersen S, Allergy 1983;38:191-194

71 children were given careful instruction in aerosol inhalation technique.

Inhalation technique was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking 2 puffs of terbutaline (each puff= 0.25 mg).

11.3

% children efficient in inhalation technique after

instruction

5-7 >7

Age (years)

100 –

80 –

60 –

40 –

20 –

0

37%

80%

Inhalation through the nose after

actuation into the mouth accounted for about 50% of

treatment failures, with the problem

being more frequent in the

younger age group.

Nasal inhalation as a cause of inefficient pulmonal aerosol inhalation technique in

children Pedersen S, Allergy 1983;38:191-194

71 children were given careful instruction in aerosol inhalation technique.

Inhalation technique was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking 2 puffs of terbutaline (each puff= 0.25 mg).

11.3

% children efficient in inhalation technique after

instruction

5-7 >7

Age (years)

100 –

80 –

60 –

40 –

20 –

0

37%

80%

When this error was corrected

about 83% of the children were efficient in the

technique.

Trick of the trade

The adequacy of inhalation of aerosol from canister nebulizers. Shim C. Am J Med 1980;69:891-4

30 patients hospitalized with asthma.

Taught the correct technique.

% patients that, when retested,

had reverted to the old incorrect technique

50%50 –

40 –

30 –

20 –

10 –

00 -

The adequacy of inhalation of aerosol from canister nebulizers. Shim C. Am J Med 1980;69:891-4

30 patients hospitalized with asthma.

Taught the correct technique.

% patients that, when retested,

had reverted to the old incorrect technique

50%50 –

40 –

30 –

20 –

10 –

00 -

Patients should be

taught repeatedly

until they learn the correct

technique and retain it !

Contributory Factors: Non-Adherence to Treatment

Hedlin G, E. RJ 2010;36:196-201

Very young children are frequently and inappropriately left to take their asthma medication unsupervised. Orrell-Valente JK, Pediatrics 2008; 122: e1186–e1192.

Finally, repeated checking of inhaler technique is important.

we learn:10% of what we read20% of what we hear30% of what we see50% of what we see and hear70% of what we say90% of what we say and do

Contributory Factors: Non-Adherence to Treatment

Hedlin G, E. RJ 2010;36:196-201

Very young children are frequently and inappropriately left to take their asthma medication unsupervised. Orrell-Valente JK, Pediatrics 2008; 122: e1186–e1192.

Finally, repeated checking of inhaler technique is important.

1)Please read2)Please do

Trick of the trade

% increase 30 minutes post salbutamol inhalation

70 -60 -50 –40 –30 –20 –10 – 0

18 asthmatic children

FEV1

FVC

Mouthpiece (MP) versus Facemask (FM) For Delivery of Salbutamol in Children With Asthma

Exacerbation. Kishida M. J Asthma 2002;39:337-9

MP FM MP FM

56.4%

28.9%34.4%

7.5%

* p<0.05

*

*

% increase 30 minutes post salbutamol inhalation

70 -60 -50 –40 –30 –20 –10 – 0

18 asthmatic children

FEV1

FVC

Mouthpiece (MP) versus Facemask (FM) For Delivery of Salbutamol in Children With Asthma

Exacerbation. Kishida M. J Asthma 2002;39:337-9

MP FM MP FM

56.4%

28.9%34.4%

7.5%

* p<0.05

*

*

Trick of the trade: train the child to

use the mouthpiece as soon as possible

How to use an MDI with a spacer


…………spray1+1 (2) spruzzi al mattino…………spray1+1 (2) spruzzi alla sera


Tira su, tira su, tira su ………………………………………………… tira su.

Inhaled corticosteroids for asthma: impact of practice level device switching on asthma

control. Thomas M, BMC Pulm Med 2009; 9: 1.

2 –

1 –

0

1.92

in the switched cohort OR for

unsuccessful treatment

p < 0.001

2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation

individually matched with patients using the same ICS device who were not switched.

Asthma control over 12 months after the switch

compared with controls

Instruct the patient to recognize the effect by the color of the device


[email protected]



WAPs should include not only instructions in case of deterioration but importantly recommendations for daily management, which remains the most effective means to prevent exacerbations in children.

Use of WAPs should be tested for their efficacy, not only in improving patient compliance and asthma control,

but

also for improving healthcare professionals’ adherence to recommendations and dispensing of the WAP.Ducharme FM, Curr Opin Allergy Clin Immunol. 2008;8(2):177-88

Definition of written action plan (WAP)

Written action plans for asthma: an evidence-based review of the key components.

Gibson GP. Thorax 2004;59:94-9.Individualised complete written action plans must containeach of the following four components of an action plan:

– when to increase treatment (action point);

– how to increase treatment;

– for how long;

– when to seek medical help.

a level of symptoms or lung function

70–85% of the personal best or pred. PEF value

Written action plan symptom-based vs PEFR 4 studies (355 ch)

Written action plan use significantly:

1) Reduced acute care visits,

2) Reduced missed school days,

3) Reduced nocturnal awakening,

4) Improved symptom scores.

Systematic review of randomized controlled trials examining written action plans in children: what is the plan? Zemek RL, Arch Pediatr Adolesc Med 2008; 162:157–

163.

1) Charlton I, BMJ.1990;301:1355.2) Wensley D, AJRCCM. 2004;170:606.3) Letz KL, Ped Asth All Immunol. 2004;17:177.4) Yoos HL, Ann All Asth Immunol. 2002;88:283

A Low-Literacy Asthma Action

Plan to Improve Provider Asthma

Counseling: A Randomized

StudyYin H S, Pediatrics.

2016;137:e20150468

A Low-Literacy Asthma Action Plan to Improve Provider Asthma Counseling: A Randomized Study

Yin H S, Pediatrics. 2016;137(1):e20150468

119 providers were randomly assigned (61 low literacy, 58 standard)

Physicians at 2 academic centers randomized to use a low-literacy or standard action plan to counsel the hypothetical parent of child with moderate persistent asthma (regimen:

-Flovent 110 μg 2 puffs twice daily, -Singulair 5 mg daily, -Albuterol 2 puffs every 4 hours as needed)

90 –80 –70 –60 –50 –40 –30 –20 –10 –00

% providers more likely to use times of day (eg, Flovent morning and

night)100 -

96.7%

p<0.001

51.7%

The low-literacy plan

Standard plan






90 –80 –70 –60 –50 –40 –30 –20 –10 –00

% providers recommend spacer use (eg Albuterol)

83.6%

p<0.001

43.1%

The low-literacy plan

Standard plan






90 –80 –70 –60 –50 –40 –30 –20 –10 –00

% providers using explicit symptoms (eg, "ribs show when breathing," )

100 -

54.1% p<0.001

3.4%The low-

literacy planStandard plan

OR=33.0

Empowering the child and caregiver: yellow zone Asthma Action Plan. Dinakar C, Curr Allergy Asthma Rep.

2014;14(11):475.

100% lung function

Symptoms’ perception


2014;14(11):475.

100% lung function

Symptoms’ perception

The yellow zone

2 weeks


2014;14(11):475. Yellow Zone Strategies:

Repetitive use of inhaled SABA (from 2 to 4 puffs to 6 to 10 puffs based on the severity of the episode)

Scheduled dosing step-up: increasing total ICS dose per 24 h (e.g., quadrupling or higher doses of ICS)

Dynamic dosing step-up: ICS along with reliever SABA use

ICS-LABA-adjustable maintenance dosing (AMD)

ICS ≥ 4 X


[email protected]

IntroductionEstablishment of a partnershipThe problem of adherenceEffective use of devicesWritten action plansEffective use of controller medicationsEffective use of quick-relief medicationsEvironment controlOxidative stress reduction and dietAddressing co-morbidities Monitoring the child asthmaSummary and Conclusions


Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid

nonadherence. Williams LK, J Allergy Clin Immunol 2011;128:1185–91.

298 asthmatics

ICS adherence estimated from electronic prescription and fill information

changes in ICS adherence over time and effect of this changing pattern of use on asthma exacerbations (need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization)

% asthma exacerbations

30 –

20 –

10 –

00 - attributable to ICS medication

non-adherence.

24%

Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid

nonadherence. Williams LK, J Allergy Clin Immunol 2011;128:1185–91.

298 asthmatics

ICS adherence estimated from electronic prescription and fill information

changes in ICS adherence over time and effect of this changing pattern of use on asthma exacerbations (need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization)

0.61

patients with adherence > 75% of the prescribed dose vs patients with adherence

≤25%

HR for asthma exacerbations

1.0 –

0.5 –

0.0

Trends in preventive asthma medication use among children and adolescents,1988-2008.

Kit BK, Pediatrics. 2012;129:62e69.

a cross-sectional analysis of preventive asthma medication (PAM) use

2499 children aged 1 to 19 years with current asthma

data from the National Health and Nutrition Examination Survey (NHANES) during 3 time periods: 1988-1994, 1999-2002, and 2005-2008.

PAMs included inhaled corticosteroids, leukotriene receptor antagonists, long-acting β-agonists, mast-cell stabilizers, and methylxanthines

compared to white children aOR of PAM use

in

0.5

1.0 –

0.5 –

0.0 non-Hispanic black

Mexican American

0.6

Trends in preventive asthma medication use among children and adolescents,1988-2008.

Kit BK, Pediatrics. 2012;129:62e69.

a cross-sectional analysis of preventive asthma medication (PAM) use

2499 children aged 1 to 19 years with current asthma

data from the National Health and Nutrition Examination Survey (NHANES) during 3 time periods: 1988-1994, 1999-2002, and 2005-2008.

PAMs included inhaled corticosteroids, leukotriene receptor antagonists, long-acting β-agonists, mast-cell stabilizers, and methylxanthines

aOR of PAM usein 12 to 19 year olds

0.5

1.0 –

0.5 –

0.0 compared to 1-11 years old children

Low Rates of Controller Medication Initiation and Outpatient Follow-Up after Emergency

Department Visits for Asthma. Andrews AL, J Pediatr 2012;160:325

Retrospective cohort study.

ED visit for asthma.

3435 patients aged 2-18 yrs.

40

–

30

–

20

–

10

–

0

% children who had a prescription for ICS after the ED visit & attended

a follow-up appointment.

5.2%




40

–

30

–

20

–

10

–

0



5.2%

Children with asthma

seen in the ED have low rates of ICS use & outpatient follow-

up.

Prescribe ICS in the ED and

organize a follow-up

visit.






40

–

30

–

20

–

10

–

0



5.2%

Children with asthma

seen in the ED have low rates of ICS use & outpatient follow-

up.

And call the patient if he is not presenting

to the follow-up visit.



Dose Response of Inhaled Corticosteroids in Children

With Persistent Asthma: A Systematic ReviewZhang L. Pediatrics 2011;127:129-38 Systematic review

and meta-analysis Randomized

controlled trials comparing ≥2 doses of ICSs

children 3-18 years with persistent asthma.

To compare moderate (300–400 μg/day) with low (≤200 μg/day BDP-equivalent) doses of ICSs.

There was no significant difference between moderate and low doses of ICSs in terms of

efficacy

Dose Response of Inhaled Corticosteroids in Children

With Persistent Asthma: A Systematic ReviewZhang L. Pediatrics 2011;127:129-38 Systematic review

and meta-analysis Randomized

controlled trials comparing ≥2 doses of ICSs

children 3-18 years with persistent asthma.

To compare moderate (300–400 μg/day) with low (≤200 μg/day BDP-equivalent) doses of ICSs.

There was no significant difference between moderate and low doses of ICSs in terms of

efficacy

Reduce the ICS dose after 3 months of

well controlled asthma.

Use the lowest ICS dose that

maintains asthma under

control.

Daily vs. intermittent inhaled corticosteroids for recurrent wheezing and mild persistent asthma:

a systematic review with meta-analysis.Rodrigo GJ. Respir Med. 2013;107(8):1133-40.

7 trials with a minimum of 8 weeks of daily ICS (daily ICS with rescue SABA during exacerbations) vs. intermittent ICS (ICS plus SABA at the onset of symptoms)

1367 participants

RR for asthma exacerbations

0.96

daily vs. intermittent ICS

1.0 –

0.5 –

0.0

Daily vs. intermittent inhaled corticosteroids for recurrent wheezing and mild persistent asthma:

a systematic review with meta-analysis.Rodrigo GJ. Respir Med. 2013;107(8):1133-40.

Pooled relative risk for percent asthma free days

Pooled relative risk for percent recue medications

If the child/parents have good perception of symptoms you can use intermittent strategy.

If not, use the daily strategy.

The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: A systematic

review and meta-analysis of randomized controlled trials

Rank MA. J Allergy Clin Immunol. 2013;131(3):724-9.

7 trials with a mean follow-up of 27 weeks

RR for an asthma exacerbation

in patients who stopped ICSs

2.35P <0.001

3 –

2 –

1 –

0 compared with those who continued

The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: A systematic

review and meta-analysis of randomized controlled trials

Rank MA. J Allergy Clin Immunol. 2013;131(3):724-9.

7 trials with a mean follow-up of 27 weeks

RR for an asthma exacerbation

in patients who stopped ICSs

2.35P <0.001

3 –

2 –

1 –

0 compared with those who continued

Provide the parents with a

symptom diary and

organize

a follow-up spirometry

within a month if you

stop treatment

182 children (6 to 17 yrs of age), who had uncontrolled asthma while receiving 100 µg of fluticasone twice daily;

16 weeks: 250 µg of fluticasone twice daily (ICS step-up), 100 µg of fluticasone plus 50 µg of a long-acting beta-agonist twice daily (LABA step-up), or 100 µg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up).

Step-up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids Lemanske

NEJM 2010;362:975

Relative probability of best response vs LTRA

step-up

1.6P=0.00

4

2 –

1 –

0 LABA step-up

Relative probability of best response vs ICS

step-up

1.7P=0.00

2

2 –

1 –

0 LABA step-up


NEJM 2010;362:975

182 children (6 to 17 yrs of age), who had uncontrolled asthma while receiving 100 µg of fluticasone twice daily;

16 weeks: 250 µg of fluticasone twice daily (ICS step-up), 100 µg of fluticasone plus 50 µg of a long-acting beta-agonist twice daily (LABA step-up), or 100 µg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up).

2X

Pairwise comparisons of the three step-up therapies


NEJM 2010;362:975

Pairwise comparisons of the three step-up therapies


NEJM 2010;362:975Always maintain a certain degree of uncertainty and evaluate objectively

the effects of your choices

Oxford University

OR for receiving ≥6 prescription

for SABA every year2 -

1 –

0

1.8

A retrospective observational study comparing rescue medication use in children on combined

versus separate long-acting β-agonists and corticosteroids

Elkout H. Arch Dis Child. 2010;95:817-21

In children reiving LABA+ICS vs LABA &

ICS

40 primary care practices for the years 2002–6

10 454 children with received at least one prescription for asthma medication

+

OR for receiving ≥6 prescription

for SABA every year2 -

1 –

0

1.8

A retrospective observational study comparing rescue medication use in children on combined

versus separate long-acting β-agonists and corticosteroids

Elkout H. Arch Dis Child. 2010;95:817-21

In children reiving LABA+ICS vs LABA &

ICS

40 primary care practices for the years 2002–6

10 454 children with received at least one prescription for asthma medication

+

Only prescribefixed-dose LABA-&-ICS

combination deevices!

Loss of asthma control in pediatric patients after discontinuation of long-acting Beta-agonists.

R O'Hagan A, Pulm Med. 2012;2012:894063.

54 children with moderate-to-severe persistent asthma after switching from combination (ICS/LABA) to monotherapy with ICS.

mean followup of 10.7 weeks

% children with loss of asthma control leading to addition of

leukotriene receptor antagonists, increased ICS,

or restarting LABA. 40 –

30 –

20 –

10 –

0

37%

Loss of asthma control in pediatric patients after discontinuation of long-acting Beta-agonists.

R O'Hagan A, Pulm Med. 2012;2012:894063.

54 children with moderate-to-severe persistent asthma after switching from combination (ICS/LABA) to monotherapy with ICS.

mean followup of 10.7 weeks

% children with loss of asthma control leading to addition of

leukotriene receptor antagonists, increased ICS,

or restarting LABA. 40 –

30 –

20 –

10 –

0

37%

Provide the parents with a

symptom diary and

organize

a follow-up spirometry

within a month if you

stop treatment

Pre-treatment by omalizumab allows allergenimmunotherapy in children and young adults

with severe allergic asthmaLambert N, Pediatr Allergy Immunol. 2014;25:829-832

Asthma control and therapeutic level for the four periods.

SCIT, Subcutaneous allergen-specific immunotherapy; BDP, Equivalent of beclomethasone dipropionate; LAT, Long-acting theophylline.

Pre-treatment by omalizumab allows allergenimmunotherapy in children and young adults

with severe allergic asthmaLambert N, Pediatr Allergy Immunol. 2014;25:829-832

Asthma control and therapeutic level for the four periods.

SCIT, Subcutaneous allergen-specific immunotherapy; BDP, Equivalent of beclomethasone dipropionate; LAT, Long-acting theophylline.

Consider the opportunity

to start immunotherapy

in a child on omalizumab

treatment.


[email protected]



Asthma Guidelines recommend early treatment of asthma exacerbation as ‘‘key in management’

Reddel HK, Am J Respir Crit Care Med. 2009;180:59-99Expert Panel Report 3: Guidelines for the Diagnosis and Management of

Asthma.

1) earlier recognition of an impending exacerbation 2) coupled with earlier augmentation of treatment at home to avoid therapy delays

A strategy to reduce exacerbations might be:

Parents report a vast number of symptoms observed

in their children before an exacerbation.• Beer S, Arch Dis Child. 1987;62:345-8.

• Rivera-Spoljaric K, J Pediatr 2009;154:877-81, e4.• Yoos HL, J Pediatr Health Care 2005;19:197-205.

• Garbutt J, Ann Allergy Asthma Immunol 2009;103:469-73.

134 children with bronchial asthma

Mean age 7.0 years (range 1-5-14 years).

A standardised questionnaire recording the symptoms that preceded the attack of asthma completed by the parents.

Prodromal features of asthmaBeer S, Arch Dis Child 1987;62:345

% children with prodromal symptoms

and/or signs

70.4% 80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

0

(95/134)

134 children with bronchial asthma

Mean age 7.0 years (range 1-5-14 years).

A standardised questionnaire recording the symptoms that preceded the attack of asthma completed by the parents.

Prodromal features of asthmaBeer S, Arch Dis Child 1987;62:345

% children with prodromal symptoms

and/or signs

70.4% 80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

0

(95/134)

Respiratory symptoms (cough, rhinorrhoea, and wheezing).

Behavioural changes (irritability, apathy, anxiety, and sleep disorders).

Gastrointestinal symptoms (abdominal pain and anorexia).

Others: fever, itching, skin eruptions, and toothache.

Parents of children (n=101) 2 to 12 years old with asthma exacerbations that required urgent care in the past 12 mo.

Telephone questionnaires to describe antecedent symptoms and signs of asthma exacerbations noticed by parents and to learn when and how parents intensify asthma treatment.

Respiratory

symptoms

24%

% Signs and Symptoms Preceding Exacerbations

Cold Behaviour

change

Other

nonspecific

symptoms

80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

0

29%

43%

79%

Detection and home management of worsening asthma symptoms. Garbutt J. Ann Allergy Asthma Immunol

2009;103:469

Cough

Treatment was Most Often Intensified When the Parent

Noticed

Shortness of

breath

Wheeze

60 –

50 –

40 –

30 –

20 –

10 –

0

55% 54%

25%




2009;103:469

Cough

Treatment was Most Often Intensified When the Parent

Noticed

Shortness of

breath

Wheeze

60 –

50 –

40 –

30 –

20 –

10 –

0

55% 54%

25%




2009;103:469

Cold is not considere

d an allarming sign by

parents !

Nonrespiratory symptoms before loss of asthma control in children. Newton L, JACI Pract 2013;1:304

Caregivers of children aged 2 to 11 years with asthma.

Diary cards daily for 16 weeks during cold and flu season.

Likert scale from 1 to 5 (3 represented baseline or usual; 1 or 2, less than usual; and 4 or 5, more than usual).

Multiple nonrespiratory (NR) Upper respiratory (UR) signs and

symptoms. Mood changes (MC) Lower respiratory tract (LR). Loss of asthma control (LOC)

Percentage of days with a nonusual symptom before

and during a LOC episode (≥2

consecutive days with LR symptoms)

Nonrespiratory symptoms before loss of asthma control in children. Newton L, JACI Pract 2013;1:304

Caregivers of children aged 2 to 11 years with asthma.

Diary cards daily for 16 weeks during cold and flu season.

Likert scale from 1 to 5 (3 represented baseline or usual; 1 or 2, less than usual; and 4 or 5, more than usual).

Multiple nonrespiratory (NR) Upper respiratory (UR) signs and

symptoms. Mood changes (MC) Lower respiratory tract (LR). Loss of asthma control (LOC)

Percentage of days with a nonusual symptom before

and during a LOC episode (≥2

consecutive days with LR symptoms) changes in behavior (moody, irritability,

tension) and appearance

(dry skin, eye swelling, sunken

eyes) can be present 3 days before an exacerbations

Difficulty in obtaining peak expiratory flow measurements in children with acute asthma.

Gorelick MH, Pediatr Emerg Care 2004;20:22-6.

65%

70 –60 -50 -40 -30 –20 –10 – 0

% of children aged 5 to 18

years able to complete PEF or FEV1 during an

exacerbation456 children (age 6-18 years old) treated in a pediatric ED for an acute exacerbation of asthma

PEFR in all children age ≥ 6 years

among children < 5 years,

these maneuvers

were almost impossible

Brown Asthma Visual Analogue ScalePictorial visual analogue scale for rating severity of childhood asthma

episodes. Fritz J. Asthma 1994;31:473

None A tiny A little Some Quite Alot Very much at all bit a bit terrible

ALB

Trick of the trade for extimating the child of perception an asthma exacerbation at home of

the child

Criteria for categorizing the severity of asthma exacerbations Camargo CA, J Allergy Clin Immunol.

2009;124(2 Suppl):S5-14


2009;124(2 Suppl):S5-14

1,2,3,4,5,6,7,8,9,10,….


2009;124(2 Suppl):S5-14

Mechanism of reduced blood pressure during inspiration During inspiration the increased negative intrathoracic pressure causes increased right sided venous return to the right atrium and, subsequently, to the right ventricle during diastole. This causes an increase in right ventricular filling pressures because of increased volume and stretch, leading to a bulging of the intraventricular septum towards the left ventricle, thus decreasing the left ventricular size and filling volume due to this protrusion. Thus, there is a subsequently decreased left sided stroke volume and therefore a lower systolic blood pressure.

+

> 20 mm Hg+

•Severe pulsus paradoxus can easily be palpated in the radial, brachial, or femoral pulses as a weakening or disappearance of the pulse during inspiration (which is usually best observed by watching the rise and fall of the abdomen).

•With a sphygmomanometer, the blood pressure is measured in the standard fashion except that the cuff is deflated more slowly than usual.

•During deflation, the first Korotkoff sound is audible only during expiration, but with further deflation additional Korotkoff sounds are clearly heard throughout the respiratory cycle. The difference between the systolic pressure at which the first beats are heard and the pressure at which all beats are heard is the size of the pulsus.

Trick of the trade measurement of pulsus paradoxus

ED MANAGEMENT OF ASTHMA EXACERBATIONS Camargo CA, J Allergy Clin Immunol. 2009;124(2 Suppl):S5-14

Dosages of drugs for asthma exacerbations

≤ 12 years of age

Caregivers of 82 children with asthma aged 4 to 14 yrs, presenting to the ED with an asthma exacerbation;

Home albuterol usewas measured using a structured interview guide.

70

–

60

–

50

–

40

–

30

–

20

–

10

–

0

Inappropriate

Appropriate

Home albuterol use for the current asthma exacerbation

was68%56/82

32%26/82

Inappropriate home albuterol use during an acute asthma exacerabtion Clayton K, Ann Allergy Asthma

Immunol 2012;109:416

69% (39/56)Undertreatin

g

Only 5% overtreating



70

–

60

–

50

–

40

–

30

–

20

–

10

–

0

Inappropriate

Appropriate


was68%56/82

32%26/82

Reasons forincorrect home albuterol use

included: no spacer (17

pts), overtreating (3

pts), overreacting (5

pts), using a controller

medicine for quick relief (6 pts).


g



Immunol 2012;109:416



70

–

60

–

50

–

40

–

30

–

20

–

10

–

0

Inappropriate

Appropriate


was68%56/82

32%26/82

In addition, most children in the entire study

population used an albuterol MDI (52%) but were giving only

2 puffs (63%)instead of 4-6-8

puffs suggested by Guidelines


g


This finding suggests some concern about

the use of albuterol at home!!!!!!!


Immunol 2012;109:416

Nota informativa importante concordata con l’Agenzia Italiana del Farmaco (AIFA)

ottobre 2014Paragrafo 4.1 Indicazioni terapeuticheBroncovaleas soluzione da nebulizzare 5mg/mL è indicato nel trattamento del broncospasmo nei pazienti di età superiore ai 2 anni…

Paragrafo 4.2 Posologia e modo di somministrazioneBambini da 2 a 12 anni: il dosaggio iniziale deve basarsi sul peso corporeo (da 0.1 a 0.15 mg/Kg per dose), con successiva titolazione fino al raggiungimento della risposta clinica desiderata.La dose non deve mai eccedere i 2.5 mg 3 o 4 volte al giorno per nebulizzazione: Peso corporeo (KG) Dose (mg) Volume di soluzione (mL) N°

gocce 10-15 1.25 0.25 5 gtt > 15 2.5 0.5 10 gtt

Cordiali saluti Valeas SPA

Nota informativa importante concordata con l’Agenzia Italiana del Farmaco (AIFA)

ottobre 2014Paragrafo 4.1 Indicazioni terapeuticheBroncovaleas soluzione da nebulizzare 5mg/mL è indicato nel trattamento del broncospasmo nei pazienti di età superiore ai 2 anni…

Paragrafo 4.2 Posologia e modo di somministrazioneBambini da 2 a 12 anni: il dosaggio iniziale deve basarsi sul peso corporeo (da 0.1 a 0.15 mg/Kg per dose), con successiva titolazione fino al raggiungimento della risposta clinica desiderata.La dose non deve mai eccedere i 2.5 mg 3 o 4 volte al giorno per nebulizzazione: Peso corporeo (KG) Dose (mg) Volume di soluzione (mL) N°

gocce 10-15 1.25 0.25 5 gtt > 15 2.5 0.5 10 gtt

Cordiali saluti Valeas SPA

?

Safety of Continuous Nebulized Albuterol for Bronchospasm in Infants and Children

Katz RW, Pediatrics 1993;92:666-9

incidence of cardiotoxicity

19 infants (mean age 20.7 ± 3.8 months) who receive continuous nebulized albuterol (CNA) for bronchospasm.

ADM=admission

Dose of albuterol during continuous

nebulization.

The Dilemma of Albuterol Dosing for Acute Asthma Exacerbations in Pediatric Patients

Arnold Chest 2011;139:472

For moderate-severity

exacerbations, six (60%) of 10 completing the

question reported using CNA doses that exceed current

expert guidelines.

Nebulized albuterol doses recommended by expert consensus guidelines for exacerbations in children ≤ 12 yrs of age are “ 0.15-0.3 mg/kg up to 10 mg every 1-4 hours as needed, or 0.5 mg/kg/hour by continuous nebulization.”

Continuous nebulized albuterol (CNA) dose (10 mg/h = 2 mL Broncovaleas sol 0.5%).

We administered an Internet-based questionnaire to respiratory care directors of the Child Health Corporation of America.

Trick of the trade with MDI use in acute asthma

Only half of patients regularly used a holding chamber with their MDI.Scarfone R, Pediatrics. 2001;108:1332e1338.

Multiple studies have demonstrated the effectiveness of albuterol delivery using a holding chamber with an MDI whencompared with using an MDI alone.Brown PH, Thorax. 1990;45:736e739.Lipworth BJ. Thorax. 1995;50:105e110.Newman SP, Thorax. 1984;39:935e941.Selroos O, Thorax. 1991;46:891e894. Camargo CA, JACI.

2009;124(2 Suppl):S5-14

Beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute

exacerbation of wheezing or asthma in children under 5 year of age: a systematic review with meta-

analysisCastro-Rodriguez JA. J Pediatr 2004;145:172-7

6 trials (n=491)

OR for hospital admission in MDI+spacer vs

nebulizers

0.42

ALL PATIENTS

0.27PATIENTS WITH

MODERATE-SEVERE EXACERBATIONS

1.00 –

0.75 –

0.50 –

0.25 –

0

Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma.

Cates CJ, Cochrane Database Syst Rev. 2013 Sep 13;9:CD000052

1897 children and 729 adults

39 trials: 33 from emergency room and community settings, 6 trials on inpatients with acute asthma

Relative Risk of hospital admission for spacer versus

nebuliser 1.0 –

0.5 –

0

0.94 0.61 to 1.43

Adults Children

0.71 0.47 to 1.08

Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma.

Cates CJ, Cochrane Database Syst Rev. 2013 Sep 13;9:CD000052

1897 children and 729 adults

39 trials: 33 from emergency room and community settings, 6 trials on inpatients with acute asthma

Relative Risk of hospital admission for spacer versus

nebuliser 1.0 –

0.5 –

0

0.94 0.61 to 1.43

Adults Children

0.71 0.47 to 1.08

The mean duration in the ED for

children given nebulised treatment

was 103 minutes,

and for children given

treatment via spacers ≤33 minutes

How do patients determine that their metered-dose inhaler is empty? Rubin BK. Chest 2004;126:1134-7

50 consecutive patients attending the Children’s Hospital Asthma Center

% patients or parents who did not know how many actuations were in their

canisters

74%75 -

60 –

45 –

30 –

15 –

0

?

Checking How Much Medicine Is Left in the Canister

A full canister will sink to the bottom. An empty canister will float on the water surface.

50 consecutive patients attending the Children’s Hospital Asthma Center

% patients or parents who did not know how many actuations were in their

canisters

74%75 -

60 –

45 –

30 –

15 –

0

?

Canister flotation was ineffective in identifying

when a pMDI was depleted,

and water obstructed the valve opening

27% of the time

How do patients determine that their metered-dose inhaler is empty? Rubin BK. Chest 2004;126:1134-7

Dose counting and the use of pressurized metered-dose inhalers: running on empty.

Sander N, Ann Allergy Asthma Immunol. 2006;97(1):34-8.

how patients evaluate the contents of their pMDI

a 6.5-minute telephone interview with a random sample of 500 families with asthma

% of bronchodilator users

reporting having been told to keep track of pMDI doses

used.

40 –

30 –

20 –

10 –

0

20%36%

reporting having found their pMDI empty during an

asthma exacerbation.

Dose counting and the use of pressurized metered-dose inhalers: running on empty.

Sander N, Ann Allergy Asthma Immunol. 2006;97(1):34-8.

how patients evaluate the contents of their pMDI

a 6.5-minute telephone interview with a random sample of 500 families with asthma

% of bronchodilator users

reporting having been told to keep track of pMDI doses

used.

40 –

30 –

20 –

10 –

0

20%36%

reporting having found their pMDI empty during an

asthma exacerbation.

82% of the patients

considered their pMDI

empty when absolutely

nothing came out !!!!!!!!!!

instruct the patient

Corticosteroids for hospitalised children with acute asthma. Smith M Cochrane Database Syst Rev. 2003;

(2):CD002886.

To determine the benefit of systemic corticosteroids (oral, intravenous, or intramuscular) compared to placebo and inhaled steroids in acute paediatric asthma.

426 children aged 1-18 yrs

7 trials

7 –

6 –

5 –

4 –

3 –

2 –

1 –

0

7.0

OR for discharge early (< 4 hrs) after admission

NNT of 3

systemic corticosteroids

Mean Asthma Control Questionnaire symptom score and mean FEV1 % pred in participants with and without subsequent acute

asthma.

AT DISCHARGE AT DISCHARGE AT FOLLOW-UPAT FOLLOW-UP

ns

ns

ns

Symptom score

FEV1 % pred

No asthm

a

No asthm

a

No asthm

a

No asthm

a

YES asthm

a

YES asthm

a

YES asthm

a

YES asthm

a

Perception of airflow obstruction in patients hospitalized for acute asthma

Davis SQ. Ann Allergy Asthma Immunol 2009;102:455-61

Mean Asthma Control Questionnaire symptom score and mean FEV1 % pred in participants with and without subsequent acute

asthma.

AT DISCHARGE AT DISCHARGE AT FOLLOW-UPAT FOLLOW-UP

ns

ns

ns

Symptom score

FEV1 % pred

No asthm

a

No asthm

a

No asthm

a

No asthm

a

YES asthm

a

YES asthm

a

YES asthm

a

YES asthm

a

Perception of airflow obstruction in patients hospitalized for acute asthma

Davis SQ. Ann Allergy Asthma Immunol 2009;102:455-61

An asthmatic patient admited to

hospital should have a spirometry

two weeks after discharge!


[email protected]



Home environment as a Contributory Factor

Hedlin G, E. RJ 2010;36:196-201

It is difficult to evaluate the home environment without visiting.

Families rarely give accurate descriptions of:

1) the degree of social deprivation and stress, 2) passive smoking, 3) house dust and pet allergen exposure, and 4) damp and mould in their homes.

Fireplaces, wood-stoves, kerosene heaters and gas for cooking have been associated with increased asthma morbidity. Belanger K, ImmunolAllergy Clin North Am 2008; 28: 507–519. Installation of more effective nonpolluting heating in the homes of children with asthma may significantly reduce symptoms. Howden-Chapman P, BMJ 2008; 337: a1411.

The importance of nurse-led home visits in the assessment of children with problematic asthma.

Bracken M, Bush A, Arch Dis Child 2009;94:780–784.

% asthmatic children with potentially modifiable factors

80 –70 –60 –50 –40 –30 –20 –10 – 0

79%Many children had multiple causes for

poor control

71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. A nurse-led hospital visit followed by a home visit.


Bracken M, Bush A, Arch Dis Child 2009;94:780–784.

% asthmatic children with potentially modifiable factors

60 –

50 –

40 –

30 –

20 –

10 –

0

59%

psychosocial factors

allergen exposure

31%

passive or active smoking

25%

medication issues including adherence

48%


Bracken M, Bush A, Arch Dis Child 2009;94:780–784.% asthmatic children that

with the home visit90 –80 –70 –60 –50 –40 –30 –20 –10 – 0

84%

23%house dust mite

avoidance measures

inadequate in those sensitised

medications not easily

available for inspection

or out of date

71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. A nurse-led hospital visit followed by a home visit.

Home environment: smoking

Hedlin G, E. RJ 2010;36:196-201

There is ample evidence from adult studies that active smoking causes steroid resistance, Chalmers GW, Thorax 2002;57:226–230.Chaudhuri R, Am J Respir Crit Care Med 2003;168:1308–1311.Livingston E, Eur Respir J 2007;29:64–71. Lazarus SC, Am J Respir Crit Care Med 2007;175:783–790. Tomlinson JE, Thorax 2005;60:282–287.

and

It is likely that passive smoke exposure has the same effects.

Physicians' Counseling of Adolescents Regarding E-Cigarette Use.Pepper JK, J Adolesc Health. 2015;57:580-6

90 –

80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

00

p<0.001

% physicians reporting routinely

screening adolescent patients for

cigarette smoking

86%

e-cigarette use

14%

776 pediatricians and family medicine physicians who provide primary care to adolescent patients completed an online survey in Spring 2014.

90 –

80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

00

p<0.001


couseling for avoiding

cigarette smoking

79%

e-cigarette use

18%



90 –

80 –

70 –

60 –

50 –

40 –

30 –

20 –

10 –

00

p<0.001


couseling for avoiding

cigarette smoking

79%

e-cigarette use

18%



Ask the adolescent

about e-cigarette use

X

Asymmetrical Peer Influence

Nonsmokers must learn

how and where to obtain cigarettes, where they can smoke without being discovered by authorities, how to conceal evidence of their smoking behavior, andmost importantly, how to smoke.

By contrast, the types of

information and other resources

required for successful

smoking cessation

knowledge of effective methods,access to smoking cessation programs access to nicotine replacement products

With a Little Help from My Friends? Asymmetrical Social Influence on Adolescent Smoking Initiation

and Cessation.Haas SA, J Health Soc Behav. 2014;55(2):126-143.

Asymmetrical Peer Influence

Nonsmokers must learn

how and where to obtain cigarettes, where they can smoke without being discovered by authorities, how to conceal evidence of their smoking behavior, andmost importantly, how to smoke.

By contrast, the types of

information and other resources

required for successful

smoking cessation

knowledge of effective methods,access to smoking cessation programs access to nicotine replacement products

With a Little Help from My Friends? Asymmetrical Social Influence on Adolescent Smoking Initiation

and Cessation.Haas SA, J Health Soc Behav. 2014;55(2):126-143.

Adolescents rarely initiate smoking without peer influence but will cease smoking while their friends continue

smoking.

Uncle Mario may be of help!

Home environment: Allergens


1) low-dose allergen exposure, even in school, can lead to deterioration of asthma control; Almqvist C, Am J Respir Crit Care Med 2001;163:694–698. Sulakvelidze I, Eur Respir J 1998;11:821–827.

2) allergen exposure and sensitisation are associated with increased severity of viral-induced exacerbations in school-age children; Murray CS, Thorax 2006;61:376–382. 3) ongoing allergen exposure in sensitised adults leads to an IL-2- and IL-4 mediated steroid resistance; Kam JC, J Immunol 1993;151:3460–3466. Nimmagadda SR, Am Rev Respir Crit Care Med 1997; 155: 87–93.

4) allergens may have non-IgE-mediated adverse effects. Langley SJ, Thorax 2005;60:17–21. Chinn S, Am J Respir Crit Care Med 2007;176:20–26.

Reduction of bronchial hyperreactivity during prolonged allergen avoidance. Platts-Mills TA, Lancet

1982; ii:675-678.

9 patients with severe aaasthma allergic to dust mites lived in hospital rooms fofor ≥ 2 months

Time course of changes in BHR to histaminein five patients showing ≥ 8 fold increase in PD30

Days with symptoms/2 weeks 1°yr 5–

4–

3–

2–

1–

0

Results of a Home-Based Environmental Intervention among Urban Children with Asthma Morgan NEJM 2004;351:1068

• 937 ch (5-11 yrs)• Controls or

Intervention groups: -covers -high efficiency vacuum cleaner -HEPA air purifier (to address multiple allergens)

• Education • Follow-up 1-2 yrs INTERVENTION CONTROL

3.394.2

P<0.00

1

% REDUCTION PER YEAR IN INTERVENTION GROUP 0 –

-10 –

-20 –

-30 -

Unscheduled visits (-2.1/yr)

-13.6% -

19.5%-20.7%

Days with symptoms (-21.3/yr)

Missed days of

school (-4.4/yr)

Results of a home-based environmental intervention among urban children with asthma

Morgan WJ, N Egl J Med 2004;351:1068

Allergen avoidance to reduce asthma-related morbidity

Sheffer AL, N Egl J Med 2004;351:1134 Editorial

“Environmental control of multiple allergens, coupled with repeated educational endeavors, can significantly reduce asthma-related complications

among inner-city children with atopic asthma.

The results are similar to those of studies evaluating the effects of corticosteroid therapy on asthma.”

≈

Effect of mattress and pillow encasings on children with asthma and house dust mite allergy.

Halken S, J Allergy Clin Immunol. 2003;111(1):169-76.

60 children (age range, 6-15 yrs) with asthma and HDM allergy

randomized to active (allergy control) or placebo mattress and pillow encasings.

After a 2-week baseline period, follow-up was performed every 3 months for 1 year.

During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose

% children who could reduce the

dose of ICS ≥ 50% after 1 year

active placebo

80 –70 –60 –50 –40 –30 –20 –10 – 0

p<0.01

24%

73%

Combination of IL-2 and IL-4 Reduces Glucocorticoid Receptor-Binding Affinity and T

Cell Response to Glucocorticoids Kam JC, J Immunology, 1993;151:3460

PBMC from normal donors and patients with Steroid Resistant asthma, cultured in the absence and presence of IL-2 andIL-4

glucocorticoid receptors (GR) dissociationconstant (Kd)

50 –

40 –

30 –

20 –

10 –

06.74

medium

alone

p=0.0001

medium (+) IL-2 & IL-4

36.1

Glucocorticoids dissociation costant

In vivo exposure to ragweed reduces the

glucocorticoid receptor binding

affinity (increases the dissociation

kostant) of peripheral blood

mononuclear cells (PBMC) from 12

atopic asthmatics.

Allergen exposure decrease glucocorticoid receptor binding affinity and steroid

responsiveness in atopic asthmatics. Nimmagadda SR, AJRCCM 1997;155:87

Before During 8 Weeks after

GCR

Kd

(nM

)

80

50

40

30

20

10

Relation to ragweed season

p < 0.001(75)

21.0

27.0

37.5

Passive Sensitization of Human Airways Increases Responsiveness to Leukotriene C4

Schmidt Eur Respir J. 1999;14:315

Contraction (change in tension) mg1000

800

600

0

400

200

10-12 10-11 10-10 10-9 10-8 10-7 10-6

Leukotriene C4 concentration M

Bronchial rings passively sensitized with IgE for mites

LC4 induced contraction

Passivelysensitized

Non sensitized

alb

Passive sensitization of bronchial rings with serum containing high IgE levels for mites

Challenged with mitesPrecontraction with

carbachol (CCh)Addition of salbutamol

Allergen Challenge of Passively Sensitized Human Bronchi Alter M2 and 2 Receptor Function

Song P, AJRCCM 1997;155:1230120

100

60

0

40

20

9 8 7 6 5 4Salbutamol concentration (-

10g M)

80

% of CCh-induced contraction

Control ()Sensitized ()

p<0.05

Sensitized and mite challenged ()

alb

Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma

model.Leclere M, Am J Respir Cell Mol Biol. 2012;47(5):589-96

Heaves-affected (a naturally occurring asthma-like disease ) adult horses with ongoing airway inflammation and bronchoconstriction

Treated with fluticasone propionate (with and without concurrent antigen avoidance) (n = 6) or with antigen (hay) avoidance alone (n = 5).

Lung function and bronchoalveolar lavage at multiple time points, and peripheral lung biopsies before and after 6 and 12 months of treatment.

Heaves is a naturally occurring disease of adult horses that shares numerous similarities with asthma, including reversible bronchoconstriction and airway inflammation when susceptible horses inhale antigens of their environment.

Coughing, wheezing, and exercise intolerance are present during clinical exacerbations, and can be controlled by antigen avoidance or corticosteroids and bronchodilators

Heaves line

Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma

model.Leclere M, Am J Respir Cell Mol Biol. 2012;47(5):589-96

Lung function improved more quickly with inhaled corticosteroids, but eventually normalized in both groups.

Inflammation was better controlled with antigen avoidance.

Airway smooth muscle remodeling decreased by approximately 30% in both groups

Heaves-affected (a naturally occurring asthma-like disease ) adult horses with ongoing airway inflammation and bronchoconstriction

Treated with fluticasone propionate (with and without concurrent antigen avoidance) (n = 6) or with antigen (hay) avoidance alone (n = 5).

Lung function and bronchoalveolar lavage at multiple time points, and peripheral lung biopsies before and after 6 and 12 months of treatment.

Allergen Avoidance

Lødrup Carlsen, Eur Respir J. 2011;37:432-40.

The value of house dust mite avoidance for asthmatic patients has been questioned, (Gotzsche PC, Allergy 2008; 63: 646–659.) but several lines of evidence suggest it may be useful in severe asthma:

First, low-dose allergen exposure, insufficient to cause acutedeterioration, may lead to steroid resistance by an interleukin(IL)-2 and IL-4 dependent mechanism. McKinley L, J Immunol 2008; 181: 4089–4097.Adcock IM, Curr Allergy Asthma Rep 2008;8: 171–178.

Secondly, the combination of viral infection, allergen sensitisation and high levels of exposure to that allergen in the home are predictive ofsevere exacerbations, and of these factors only allergen exposure is amenable to intervention. Murray CS, Thorax 2006; 61: 376–382.


[email protected]



Smoke & Pollution Exposure and Epigenetics

Rahman I , Eur Respir J . 2006;28:219-242 .

1) by altering nuclear factor kB (NF- kB) activation or

2) by histone modification and

3) chromatin remodeling

•allergic reactions•infections•cigarette smoke •air pollution

overexpression of proinflammatory genes

Oxidative stress

epigenetic effects

Moreno-Macias H, JACI 2014;133:1237

Oxidative stress in allergies and asthma prevalence

Some researchers have proposed that the increased prevalence of allergic diseases is a consequence of decreasing intake of antioxidants as people adopt Western diets characterized by a reduced amount of fresh fruits and vegetables. Allan K, Clin Exp Allergy 2009;40:370-80.

Others have suggested that it is linked to the increased consumption of processed and oxidants enriched foods.Feary J, Thorax 2007;62:466-8.

(-)

(+)

Increased exhaled 8-isoprostane in childhood asthma.

Baraldi E, Chest. 2003;124(1):25-31.

12 healthy children, 12 steroid-naïve asthmatic children, 30 children in stable condition with mild-to-moderate persistent asthma treated with inhaled corticosteroids (ICSs) [average dose, 300 micro g per day]exhaled breath condensate (EBC),

8-isoprostane levels in EBC(marker of lipid peroxidation)

ns

Urinary Bromotyrosine Measures Asthma Control and Predicts Asthma Exacerbations in Children

Wedes, J Ped 2011;159:248

Urinary bromotyrosine, a non invasive marker of eosinophil-catalyzed protein oxidation.


Follow-up 6 weeks.ORs and 95% CI for the associations between high levels of bromotyrosine and nitric oxide and uncontrolled asthma at

baseline

in asthmatic

airways Oxidative

Stress

Asthma and the REDOX System

1) peroxidation of lipids, proteins, and DNA

2) production of chemoattractants,

3) BHR, 4) airway secretion,5) vascular permeability,

increases

Barnes Free Rad Biol Med 1990;9:235. Rahman I. J Biochem Mol Biol 2003;36:95.Henderson WR J Immunol 2002;169:5294.ROS also

promote the activities of

6) proinflammatory redox-sensitive nuclear factors, (NF-kB).

thus increasing the allergic inflammation

Histone deacetylase-2 and airway disease.Barnes PJ. Ther Adv Respir Dis. 2009;3:235-43.

whereas histone

deacetylase-2 (HDAC2) suppresses

inflammatory gene expression.

increased expression of inflammatory genes

suppresses inflammatory gene

expression


whereas histone





expression

The reduction in HDAC2 appears to be secondary to

increased oxidative stress in the lungs.


whereas histone





expression

The reduction in HDAC2 appears to be secondary to

increased oxidative stress in the lungs.

Antioxidants such as

curcumin may therefore restore

corticosteroid sensitivity

Serum heavy metal and antioxidant element levels of children with recurrent wheezing.Razi CH, Allergol Immunopathol (Madr). 2011;39:85-9.

Correlation between serum zinc levels and

n° of Acute Respiratory Tract Infections.

r:−0.332, p = 0.001

100 children with recurrent wheezing from 1 to 6 years

116 age- and sex- matched healthy children.

serum mercury, lead, aluminium, zinc, selenium, and copper levels in blood

Serum heavy metal and antioxidant element levels of children with recurrent wheezing.Razi CH, Allergol Immunopathol (Madr). 2011;39:85-9.

Correlation between serum zinc levels and n° of wheezy attacks during the previous

year

r:−0.776, p < 0.001

100 children with recurrent wheezing from 1 to 6 years

116 age- and sex- matched healthy children.

serum mercury, lead, aluminium, zinc, selenium, and copper levels in blood

Zinc status in infantile wheezing.Tahan F, Pediatr Pulmonol. 2006;41:630-4.

Wheezy infants (n = 34) Healthy children (n = 14)

Levels of zinc in hair 34

140 –120 –100 -800 -600 –400 –200 – 0

Wheezing

ControlsCHILDREN

WITH

136.5

Hair zinc level (μg/g hair)

p<0.001

A normal hair zinc range is around 150 - 240µg/gram. Levels of < 70µg/gram would be

indicative of zinc deficiency.

Erythrocyte zinc levels.

67 asthmatic and

45 healthy children.

Mean concentrations (μg/dl) of erythrocyte zinc in children hospitalized for an asthma attack in the previous 12

mo.

NO YES

12481300 –

1200 –

1100 –

1000

1095

p<0.0001

Erythrocyte zinc levels in children with bronchial asthma.

Arik Yilmaz E, Pediatr Pulmonol. 2011;46(12):1189-93.

Erythrocyte zinc levels.

67 asthmatic and

45 healthy children.

Mean concentrations (μg/dl) of erythrocyte zinc in children hospitalized for an asthma attack in the previous 12

mo.

NO YES

12481300 –

1200 –

1100 –

1000

1095

p<0.0001

Erythrocyte zinc levels in children with bronchial asthma.

Arik Yilmaz E, Pediatr Pulmonol. 2011;46(12):1189-93.

Zalewski PD. J Nutr Immun 1996;4:39–101.Arm JP, Am Rev Respir Dis 1989;139:1395–1400.

Kadrabova J, J Trace Elem Med Biol 1996;10:50–53.Richter M, Chest 2003;123:446.

It is possible that zinc supplementation may decrease the

risk for persistent wheezing in children

% children with acute lower respiratory

infections during 180 days follow-up

The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial. Shah UH,

Clin Nutr. 2013;32:193

60 –

50 –

40 –

30 –

20 –

10 –

0

20.8% P=0.009

45.8%

Zinc Placebo

96 children living in India

10 mg zinc gluconate or placebo for 60 days.

Follow-up: 180 days.

supplementation

Effect of zinc supplementation in children with asthma:

a randomized, placebo-controlled trial in northern Islamic Republic of Iran.

Ghaffari J, East Mediterr Health J. 2014;20(6):391-6

284 children on ICS

zinc supplements (50 mg/day) (n = 144 cases) or placebo (n = 140 controls) for 8 weeks

130 -120 -110 –100 –090 –080 –070 –060 –050 –040 –030 –020 –010 –000

serum zinc concentrations (μg/dL)

61.8 60.9

baseline after supplementation

129

63

Effect of zinc supplementation in children with asthma:

a randomized, placebo-controlled trial in northern Islamic Republic of Iran.

Ghaffari J, East Mediterr Health J. 2014;20(6):391-6

284 children on ICS

zinc supplements (50 mg/day) (n = 144 cases) or placebo (n = 140 controls) for 8 weeks

130 -120 -110 –100 –090 –080 –070 –060 –050 –040 –030 –020 –010 –000

serum zinc concentrations (μg/dL)

61.8 60.9

baseline after supplementation

129

63

The case group showed significant improvements in clinical symptoms

such as cough, wheezing and

dyspnoea

and in all spirometry

parameters (FVC, FEV1 and

FEV1/FVC).

Can Fam Physician. 2009;55:887-9

Magnesium is the fourth most abundant ion in the human body Magnesium has a role in:

- relaxation of bronchial cells ( decreasing intracellular calcium by blocking its entry, and inhibiting its interaction with myosin), - stabilizes T cells - inhibits mast cell degranulation, leading to a reduction in inflammatory mediators., - depresses muscle fibre excitability by inhibiting acetylcholine release in cholinergic motor nerve terminals. - stimulates nitric oxide and prostacyclin synthesis, which might reduce asthma severity

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-

controlled trial. Gontijo-Amaral C, Eur J Clin Nutr 2007;61:54-60.

Asthmatic children and adolescents who received oral magnesium supplementation

(MG) during 2 months presented fewer days of asthma exacerbation episodes and

inhaled salbutamol compared to placebo control group (PC).

37 childrenmagnesium 300 mg/day (n=18,) and placebo (n=19), for 2 months

inhaled fluticasone (250 цg twice a day) and salbutamol as needed

methacholine challenge test (PC20).

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-

controlled trial. Gontijo-Amaral C, Eur J Clin Nutr 2007;61:54-60.

After 2 months of magnesium supplementation, the PC20 methacholine was significantly higher in the magnesium

group (MG) compared to the placebo control group (PC)

37 childrenmagnesium 300 mg/day (n=18,) and placebo (n=19), for 2 months

inhaled fluticasone (250 цg twice a day) and salbutamol as needed

methacholine challenge test (PC20).

Selenium

The selenium content in foods depends on the concentration of selenium in the soil where the crops were grown.

The following foods are generally considered good sources of selenium:

Brazil Nuts Sunflower SeedsFish (tuna, halibut, sardines, flounder, salmon)Shellfish (oysters, mussels, shrimp, clams, scallops) Meat (Beef, liver, lamb, pork)Poultry (chicken, turkey)EggsMushrooms (button, crimini, shiitake)Grains (wheat germ, barley, brown rice, oats)Onions

Selenium•Selenium has a stimulator effect on the Th1 immune response against viral infections, and its deficiency affects the occurrence, virulence, or disease progression of some viral infections.Kremidjian-Schumacher L, Biol Trace Elem Res 1994; 41: 115-127.Taylor EW, Biol Trace Elem Res 1997; 56: 63-91.Beck MA, FASEB J 2001; 15: 1481-1483.

•In human volunteers suboptimal selenium status is associated with increased replication and delayed clearance of live attenuated polio vaccine because of reduced and delayed CD31 T lymphocyte proliferative and interferon-γ responses. Broome CS, Am J Clin Nutr 2004;80:154–62.

reduced plasma selenium status may impair the ability of immune

system to mount an effective response to viral infection,

increased risk of severe protracted wheeze.

Hair Zinc and Selenium Levels in ChildrenWith Recurrent Wheezing

Razi C. H., Pediatr Pulmonol 2012;47:1185–1191

Zn and Se hair levels

Total antioxidant capacity (TAC) (mmol/L)

65 patients with recurrent wheezing (RW)

65 healthy children (HC)

300 –

200 –

100 –

000

162

236

217

280

RW HC RW HC

P < 0.001 P < 0.001

Zn SeHair levels

(μg/g)

Hair Zinc and Selenium Levels in ChildrenWith Recurrent Wheezing

Razi C. H., Pediatr Pulmonol 2012;47:1185–1191

Zn and Se hair levels


65 patients with recurrent wheezing (RW)

65 healthy children (HC)

2.0 –

1.5 –

1.0 –

….0


RW group

1.38

HC group

1.53

P < 0.001

A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent

leukotriene synthesis. Kalhan R, Clin Exp Allergy. 2008;38:103.

A dietary supplementation with 35 mg of soy genistein daily for 4 weeks in asthma patients results in reduced ex vivo synthesis of leukotriene C4 (LTC4) by eosinophils and reduced fraction of exhaled nitric oxide (FeNO).

LTC4 by eosinophils FeNO

p=0.02 p=0.03

47 asthmatic children (moderate-severe GINA Guidelines) (12.01 ± 3.1 years)

admitted to Istituto Pio XII, Misurina (m 1753)

Supplementation for 1 mo with a mixture of nutraceuticals: soy genistein, curcumin, resveratrol, vitamin D, zinc, magnesium, selenium, folic acid (n=15) or controls (n=32)

FeNO expressed as median values

9%

Anti-oxidants supplementation reduces FeNOin children with asthma.

Tenero L. Allergy Asthma Proc. 2016;37(1):8-13.

ns

P=0.03

18 16

1911

Controls

47 asthmatic children (moderate-severe GINA Guidelines) (12.01 ± 3.1 years)

admitted to Istituto Pio XII, Misurina (m 1753)

Supplementation for 1 mo with a mixture of nutraceuticals: soy genistein, curcumin, resveratrol, vitamin D, zinc, magnesium, selenium, folic acid (n=15) or controls (n=32)

FeNO expressed as median values

9%

Anti-oxidants supplementation reduces FeNOin children with asthma.

Tenero L. Allergy Asthma Proc. 2016;37(1):8-13.

ns

P=0.03

18 16

1911

Controls

Future Research

Antioxidants?

(-)(+)

Transcription factors are proteins that bind to DNA controlling

the transcription of messenger RNA

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCNSX7cff6ccCFUh-GgodMtYHCQ&url=http://www.anti-agingfirewalls.com/2013/10/28/the-master-regulator-of-aging-redox-glutatione-and-cysteine-part-1/&psig=AFQjCNHbxWyu6aBHRc0EYtGg1uep39KJKQ&ust=1441881029346472

http://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCI_Usc_Q7scCFcNXGgodKjsDGw&url=http://www.dailyperricone.com/2011/02/start-fresh-sulforaphane/&psig=AFQjCNFzS9fqfjBnrQmUSXsGdjAImGpTWA&ust=1442048811411456

Dietary intake of soy genistein is associated with lung function in patients with asthma.

Smith, J Asthma 2004;41:833.

1033 asthmatics, aged 12-75 years. Food frequency questionnaire (intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber )

100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0

FEV1 % predicted

82.1%

p=0.006

genistein consumers of

≥250 μg/1000 Kcal/day 0 μg/1000 Kcal/day

76.2%

300 asthmatics. Level of soy genistein

intake (little or no intake, moderate intake, or high intake).

Lung function and asthma control.

6-month follow-up period.

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective

multicentre clinical trialBime C, Prim Care Respir J 2012 ;21:398

54%

little or no

genistein

60 –

50 –

40 –

30 –

20 –

10 –

00

40%35%

P<0.001

moderate

high

% patients with asthma exacerbations

soy genistein intake

>1500μg/day>10μg/day

Curcumins-rich curry diet and pulmonary function in Asian older adults. Ng TP, PLoS One.

2012;7(12):e517532,478 Chinese adults aged ≥ 55 years in the Singapore Longitudinal Ageing Studies.curry intake and spirometry

FEV1, FVC and FEV1/FVC% by levels of curry intake.

Efficacy of high-dose vitamin D in pediatric asthma:

A systematic review and meta-analysis.Pojsupap S. J Asthma. 2014 Nov 3:1-29. [Epub ahead of print]

Clinical trials reporting asthma-related respiratory outcomes following vitamin D administration at a dose ≥ 500 IU per day

5 trials

The median trial size was 48 participants (range 17-430)

The average daily dose of cholecalciferol ranged from 500 to 2,000 IU/day.

RR for asthma exacerbation1.0 –

0.5 –

0 in asthmatics who had been vitamin D supplemented

0.41

Vitamin D and respiratory tract infections: A systematic review and meta-analysis of

randomized controlled trials. Bergman P, PLoS One 2013; 8:e65835

meta-analysis of 11 placebo-controlled studies

5660 patients included 0.64

OR for respiratory tract infection

1.0 –

0.5 –

0.0

in vitamin D supplemented



0.51

vitamin D supplemented in


1.0 –

0.5 –

0.0 daily doses vs bolus doses

0.86

P=0.01


5660 patients included



0.51



1.0 –

0.5 –


0.86

P=0.01



Intermittent bolus dosing with long lag

times (greater than 3–4 weeks) leads to wide swings in circulating

levels of 25 OHD, which in turn leads to dips in tissue levels of 1,25

dihydroxy D, leading to a relative excess of the catabolic enzyme 24

hydroxylase.



0.51



1.0 –

0.5 –


0.86

P=0.01



This mechanism has also been suggested

to be operating in elevating the risk for some cancers due to wide fluctuations in circulating vitamin D

levels.Weiss S.Thorax 2015;70:919-920

Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients. Xystrakis E, J Clin Invest

2006;116:146–155.adding vitamin D to cell cultures increases glucocorticoid-induced

secretion of IL-10 by Tregs

Patients with severe asthma failling to demonstrate clinical improvement upon glucocorticoid therapy (steroid resistant = SR)

Dexamethasone does not enhance secretion of IL-10 by their CD4+ T cells


[email protected]



Assessing Comorbidities and Contributory Factors

1) Rhinosinusitis/(adults) nasal polyps2) Psychological factors: personality trait, symptom perception, anxiety, depression3) Vocal cord dysfunction, Hyperventilation syndrome4) Obesity5) Smoking/smoking related disease6) Obstructive sleep apnoea7) Allergen exposure including foods8) Hormonal influences: premenstrual, menarche, menopause, thyroid disorders9) Gastro-oesophageal reflux disease (symptomatic)10) Drugs: aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), β-adrenergic blockers, angiotensinconverting enzyme inhibitors


Assessing Comorbidities and Contributory Factors

1) Rhinosinusitis/(adults) nasal polyps2) Psychological factors: personality trait, symptom perception, anxiety, depression3) Vocal cord dysfunction, Hyperventilation syndrome4) Obesity5) Smoking/smoking related disease6) Obstructive sleep apnoea7) Allergen exposure including foods8) Hormonal influences: premenstrual, menarche, menopause, thyroid disorders9) Gastro-oesophageal reflux disease (symptomatic)10) Drugs: aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), β-adrenergic blockers, angiotensinconverting enzyme inhibitors

That other conditions may coexist with asthma should always be borne in mind,

since continuing respiratory

symptoms may be wrongly attributed to asthma alone.


ED VISIT

IN PRESENCE OF MODERATE SEVERE-RHINITIS OR FOR

UNCONTROLLED ASTHMA

<10% BRONCHODILATION AFTER SALBUTAMOL

3.83

12.68

2.94

15 –

10 –

5 –

0

Lack of Control of Severe Asthma is Associated with

Co-existence of Moderate-to-Severe Rhinitis Ponte EV, Allergy 2008;63:564

Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and

pulmonary function.Dixon AE Chest. 2006;130:429-35.

2,031 asthmatics

presence of sinusitis

6 -

5 –

4 –

3 –

2 –

1 –

0

5.7

sinusitis

n° exacerbations/patient/year

YES NO

3.7

P<0.01

Chronic sinusitis in severe asthma is related to sputum eosinophilia. ten Brinke A, J Allergy Clin Immunol

2002;109:621–6.

Chronic sinusitis in severe asthma is related to sputum eosinophilia. ten Brinke A, J Allergy Clin Immunol

2002;109:621–6.

nasal irrigation use in the treatment of pediatric CRS can be part of the

treatment in severe asthmatics

Pham V, Laryngoscope. 2014;124:1000-7. Isaacs S, Am J Rhinol Allergy. 2011;25:e27-9.

Evaluation of airway hyperresponsiveness in chronic rhinosinusitis: values of sinus computed

tomography Chen Ann Allergy 2014;113:609

Olfactory cleft (OC) score was observed on the posterior ethmoid sinus and superior turbinate.

Each OC score was 0.

Left OC score was 2, right OC score was 0, total OC score was 2.

Each OC score was 1, total OC score was 2.

Each OC score was 2, total OC score was 4.

BHR

0 0 02

2 21 1

Comorbidities: Gastro-oesophageal reflux

Hedlin G, E. RJ 2010;36:196-201

The relationship between the oesophagus and the lung is complex.

Lung disease can cause gastro-oesophageal reflux, reflux can cause lung disease or reflux may be of no clinical significance.

Depending upon the criteria used for diagnosis, 25–80% of children with chronic respiratory disease have gastro-oesophageal reflux. Bechard DE, Gastroenterology 1998; 114: 849–850

A precise mechanistic link between gastro-oesophageal reflux and decline in asthma control has not been established. Stordal K, Arch Dis Child 2005; 90:956–960. ERS/ATS Guidelines, ERJ 2014;43:343-373

Systematic review: the extra-oesophageal symptoms of gastro-oesophageal reflux disease

in children.Tolia V, Aliment Pharmacol Ther 2009;29:258–272.

prevalence of GERD in children with asthma

18 relevant articles

pooled weighted average prevalence of GERD in

healthy

70 –

60 –

50 –

40 –

30 –

20 –

10 –

0

4.0% 23.0%asthmatics

19.3%

65%

range

respiratory symptoms,

sinusitis and dental erosion

were significantly more prevalent in

children with GERD than in controls.

Comorbidities: Gastro-oesophageal reflux

The role of ‘‘silent’’ GOR disease (GORD) as a cause of poor asthma control in general may be over-emphasised,

but

the child with gastrointestinal symptoms and problematic asthma should be evaluated and treated for GORD.•Holbrook JT, JAMA 2012; 307: 373–381.


Comorbidities: Obesity

Hedlin G, E. RJ 2010;36:196-201

The relationship between obesity and asthma is complex.

There are a number of confounding factors:

Obesity causes

gastro-oesophageal reflux

obstructive sleep apnoea.

Beuther DA, AJRCCM

2006;174:112–119.

reduction in respiratory system compliance, lung volumes (ERV, FRC, TV), and peripheral airway diameter,

increase in BHR,

alteration in pulmonary blood volume, and ventilation–perfusion mismatch.

Lung volumes in obesity

deep inhalation effect

Obesity and Asthma.Beuther DA. Am J Respir Crit Care Med. 2006;174:112-9.

In obesity, visceral adiposity is correlated with circulating levels of proinflammatory cytokines, and adipose tissue propagates inflammation both locally and systemically, in part through recruitment of macrophages via chemokines such as monocytechemoattractant protein-1 (MCP-1) and in part via elaboration of proinflammatory cytokines and chemokines such as:

leptin, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), transforming growth factor 1 (TGF-1), eotaxin.

Body mass and glucocorticoid response in asthma.

Sutherland ER, Am J Respir Crit Care Med 2008;178:682–687.

reduced induction in obese asthmatics

A total of 45 nonsmoking adults, 33 with asthma (mean FEV1% PRED = 70.7%) and 12 without asthma

Dexamethasone (DEX, 10-6)M)-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) a negative regulator of proinflammatory cytokines and baseline tumor necrosis factor (TNF)-alpha expression evaluated by polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage cells

Comorbidities: Dysfunctional Breathing


mimic asthma, or, more usually, complicate the assessment of a known asthmatic

vocal cord dysfunction, hyperventilation and other forms of dysfunctional breathing

1) The disappearance of these symptoms when the child is

asleep is a useful pointer, and 2) asking the family to video an attack may also be useful.

may

Seear M, Arch Dis Child 2005;90:898–902.Van Dixhoorn DJ, J Psychosom Res 1985;29:199–206.

Prevalence of Dysfunctional Breathing in Patients Treated for Asthma in Primary Care: Cross Sectional Survey Thomas BMJ 2001; 322: 1098

219 adult asthmatics

Nijmegen questionnaire (+) when score >23

% ASTMATIC PATIENTS30 –

20 –

10 –

0Nijmegen SCORE >23

29%

Comorbidities: Dysfunctional Breathing: Hyperventilation

De Groot EP, Eur Respir J 2010;36:671-78

There is no accepted goldstandard of the diagnosis of dysfunctional breathing beyond the clinical description, but the Nijmegen Questionnaire is asymptom checklist that can be used to discriminatedysfunctional breathers from normal individuals in adults.

van Dixhoorn DJ, J Psychosom Res 1985; 29: 199–206.

>23

Nijmegen score distribution in subjects with asthma and no asthma

Hyperventilation Syndrome in Adolescents with and without Asthma

D’Alba I, de Benedictis F M. Ped Pul 2015;50:1184–1190

Use of Videography in the Diagnosis of Exercise Induced Vocal Cord Dysfunction (EIVCD):

A Case Report with Video Clips.Davis JACI 2007;119:1329

NORMAL VCD

The effort on the right reveals blunting or flattening of the inspiratory portion of

the loop.

In evaluating for EIVCD, an exercise challenge with flow-volume loops may show the characteristic pattern of a flattening or clipping of the inspiratory loop (ending of the inspiratory limb below total lung capacity) when the patient is symptomatic.

VolumeFl

ow (

L/se

c)

O2 AND CO2 EQUATIONS Snider CHEST 1973; 63: 801

Alveolar-arterial oxygen difference

Normal values in normal young person = 8 torr at age 75 years = 17 torr at age > 75 = 24 torr

P(A-a) O2 = PA O2 - Pa O2 PAO2= 150 – (PaCO2 X 1.25)

150 if in air, otherwise O2 % X 7

The P(A-a) O2 in asthmatic exacerbations ranges from 30 to 59 mmHg (torr) McFadden NEJM 1968;278:1027

Comorbidities: Mental disorders

De Groot EP, Eur Respir J 2010;36:671-78

Childhood depressive illnesses, including major depressive disorder and dysthymia, are recurrent, often chronic conditions with significant morbidity and mortality. Ford T, J Am Acad Child Adolesc Psychiatry 2003;42:1203–1211.Galil N. Curr Opin Pediatr 2000;12:331–335.

Population studies of children and adolescents in the USA and in Europe have reported prevalence rates of depression ranging between 0.14% and 2.5% in children and 0.45 to 8.3% in adolescents. Ford T, J Am Acad Child Adolesc Psychiatry 2003;42:1203–1211.Galil N. Curr Opin Pediatr 2000;12:331–335.Sorensen MJ, Ugeskr Laeger 2006;168:679–682.

dysthymia

The prevalence of DSM-IV anxiety and depressive disorders in youth with asthma compared with

controls. Katon W, J Adolesc Health 2007;41:455–463.

Telephone interview to all youth aged 11-17 years with asthma (N = 781) and a random sample of similar aged controls (N = 598)

Diagnostic Interview Schedulefor Children (C-DISC-4.0) to diagnose anxiety and depressive disorders

Questionnaires to assess severity of anxiety and depressive symptoms

% children who met DSM-IV criteria for ≥ 1 anxiety and depressive

disorders

asthmatics

20 –

15 –

10 –

15 –

0

8.6%

p<0.01

healthy

16.3%(OR=1.92)

The prevalence of DSM-IV anxiety and depressive disorders in youth with asthma compared with

controls. Katon W, J Adolesc Health 2007;41:455–463.

Telephone interview to all youth aged 11-17 years with asthma (N = 781) and a random sample of similar aged controls (N = 598)

Diagnostic Interview Schedulefor Children (C-DISC-4.0) to diagnose anxiety and depressive disorders

Questionnaires to assess severity of anxiety and depressive symptoms

living with a single-parent

2 –

1 –

1

0 female gender

OR for meeting criteria for ≥ 1 anxiety or depressive disorders

1.96 1.96

Quality of mental health care for youth with asthma and comorbid anxiety and depression.

Katon WJ, Med Care 2006;44:1064–1072.

rate of recognition of Diagnostic and Statistical Manual of Mental Disorders, edition IV, anxiety and depressive disorders

quality of mental health care provided for 133 adolescent with asthma and comorbid anxiety and/or depression during the 12-month period prior to diagnosis.

% adolescents with asthma and comorbid anxiety and/or depression

recognized by the medical system during a 12-month period.

50 –

40 –

30 –

20 –

10 –

0

35.0%43.0%

with ≥ 1 anxiety and

depressive disorders

with majordepressive disorders

General red flags, which may indicate that a teen needs help:

Excessive sleeping beyond your child’s normal fatigue or insomniaSudden changes in academic performanceDramatic changes in eating habitsLoss of interest in normal activitiesSocial isolationChanges in personality (becomes more aggressive, angry, withdrawn, etc.)

Teens often experience shifts in mood and temperament, and everyone is subject to feeling sad and/or overwhelmed at times. However, sometimes your teen’s mood swings may be caused by something other than a bad grade or a nasty breakup.


[email protected]



Disagreement between skin prick test and specific IgE

in young children Schoos A. M. M. Allergy 2015;70:41

389 children from the Copenhagen Prospective Study on Asthma in Childhood

SPTs and sIgE levels assessed simultaneously for 16 common inhalant and food allergens at age ½, 1½, 4, and 6 years

Inhalant allergens: changes in prevalence over

time

Inhalant allergens: changes in prevalence over time

Disagreement between skin prick test and specific IgE

in young children Schoos A. M. M. Allergy 2015;70:41

The prevalence of inhalant allergen sensitization increased during childhood diagnosed by both sIgE levels (p<0.0001) and SPT results

(p<0.0001)

Bush A, Eur Respir J 2011;38:947-958

Diagnosis of Fungal Sensitization

If a diagnosis of severe asthma with fungal sensitisation (SAFS) is being considered, sensitisation should be tested both with SPT and sIgE since concordance between the two varies from 70 to 80%.

SAFS is diagnosed in a patient of any age with evidence ofsensitisation on either SPT or sIgE to at least one fungus(table 1).

•Denning DW, Am J Respir Crit Care Med 2009;179:11–18.•Frith J, Clin Exp Allergy 2011; 41:948–953. +

A population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood.

A machine learning approach to cluster children into multiple atopic classes in an unsupervised way.

Kaplan-Meier estimates of cumulative risk of hospital admission with

wheeze or asthma during the first 8 yrs of life stratified on five-class

model.

+

Beyond Atopy: Multiple Patterns of Sensitization in Relation to Asthma in a Birth Cohort Study

Simpson AJRCCM 2010;181:1200

http://www.moldbacteria.com/Alternaria_alternata.gif

High titers of IgE antibody to dust mite allergen and risk for wheezing among

asthmatic children infected with rhinovirus. Soto-Quiros, JACI 2012;129:1499

Children (7- 12 years). 96 with acute

wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects.

Rhinovirus strains in nasal washes.

Allergen-specific IgE.sIgE for mites ≥ 17.5

IU/ml and (+) for rhinovirus

35.5

OR for wheezing40 –

30 –

20 –

10 –

0

p<0.001+

Childhood Allergic Asthma Is Not a Single Phenotype

Just J, J Ped 2014;164;815-820 IgE-mediated allergic

asthma phenotype appears to be heterogeneous

allergic phenotypes in 125 children (average age 8.9 years) by cluster analysis

18 variables were analyzed: sex and age, eczema and food allergy, asthma duration, asthma severity and control, severe exacerbations, total IgE level, allergic sensitization, fractional exhaled nitric oxide, and functional parameters

Four clusters were identified in 125 children:

(1) 57 (45.6%)children constituted the “House dust mite Sensitization and Mild Asthma” cluster(2) 12 (9.6%) children had “Pollen Sensitization with Severe Exacerbations,”(3) 20 (16%) children had “Multiple Allergies and Severe Asthma,(4) 36 (28.8%) children had “Multiple Allergic Sensitizations and Mild Asthma”

Environmental changes could enhance the biological effect of Hop J pollens on human airway

epithelial cellsLee SI, J Allergy Clin Immunol 2014;134:470

Occludin degradations induced by Hop J pollen extracts.

Visualized by immunocytochemistry

ROS production induced by the 98 and 09 extracts

Exposure to an Aeroallergen as a Possible Precipitating Factor in Respiratory Arest in Young

Patients with Asthma O’ Hollaren N Engl J Med 1991;324:359

SPT and sIgE to Alternaria.11 pts (11-25 years) with respiratory arrest 99 asthmatic controls with no sudden respiratory arrest.

90 –80 –70 –60 –50 –40 –30 –20 –10 –00

100 -

31%

p<0.001

% subjects sensitive to Alternaria

Respiratory arrest

Controls

91%

(10/11)

OR=189.5

Fungal sensitization

FEF25–75% pred

90 –80 –70 –60 –50 –40 –30 –20 –10 –00

100 -

X%

No fungal sensitization

p=0.004

FEV1 % pred FEV1/FVC

81.5%

95.5%

71.5%

83%

55%

78.5%

p=0.016p=0.002

Fungal sensitization in childhood persistent asthma

is associated with disease severity Vicencio A. G. Ped Pulmonology 2014;49:8–14

64 children with moderate to severe persistent asthma

Prevalence of fungal sensitization

Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study.

Roberts G, J Allergy Clin Immunol 2003;112:168–174.

A case-controlled design, 19 children (1-16 years) ventilated for an exacerbation of asthma were enrolled.

Each case was matched by sex, age, and ethnicity, with 2 (38) controls who had attended with a non-life-threatening exacerbation.

In children ventilated for an exacerbation of asthma compared with

non-ventilated OR for 9 –8 –7 –6 –5 –4 –3 –2 –1 –0

10 -

9.85

frequent admission with asthma

food allergy

5.89

Lung function

A BDR cutoff of 8% or less performed significantly better than a cutoff of 12% (P = 0.03, 8% vs 12%) in the CAMP

study.

% of sick people who are correctly identified as having the condition

% of healthy people who are correctly identified as not having the condition

Diagnostic accuracy of the bronchodilator response

in children. Tse SM, JACI 2013;132:554 CAMP study: 1041 children with asthma

mean BDR as the percentage change in FEV1 in consistent

responders (solid line) versus nonresponders (dashed line)

Clinical predictors and outcomes of consistentbronchodilator response (BDR) in the childhood

asthma management program. Sharma S. JACI 2008;122:921-8

1041 participants in the CAMP, subjects with a change in FEV1 of 12%or greater (and 200 mL) after inhaled β2-agonist administration at each of their yearly follow-up visits (consistent BDR) those who did not have a consistent BDR.

1041 participants in the CAMP, subjects with a change in FEV1 of 12%or greater (and 200 mL) after inhaled b2-agonist administration at each of their yearly follow-up visits (consistent BDR) those who did not have a consistent BDR.

mean BDR as the percentage change in FEV1 in consistent

responders (solid line) versus nonresponders (dashed line)this

phenotypeis

associated with poor

clinical outcomes.

Clinical predictors and outcomes of consistentbronchodilator response (BDR) in the childhood

asthma management program. Sharma S. JACI 2008;122:921-8

Classifying asthma severity in children: mismatch between symptoms, medication use, and lung

function.Bacharier LB, Am J Respir Crit Care Med 2004; 170:426–432.Questionnaire completed by parent and child prior to physician

visit.


function.Bacharier LB, Am J Respir Crit Care Med 2004; 170:426–432.

Parents of children aged 5-18 years with asthma completed questionnaires regarding asthma medication use and symptom frequency over the preceding 1 and 4 weeks, respectively.

All children performed spirometry.

Classification of asthma severity based

on symptom frequency or medication use 50 –

40 –

30 –

20 –

10 –

06.9%mild

intermittent mild

persistent

27.9%

moderate persistent

22.4%

severe persistent

42.9%


function.Bacharier LB, Am J Respir Crit Care Med 2004; 170:426–432.mean % pred. FEV1 in children with different asthma

severity90 –80 –70 –60 –50 –40 –30 –20 –10 –00

100 -

97.5%

mild intermittent

mild persistent

moderate persistent

severe persistent

101.1% 99.9% 95.1%ns ns ns


function.Bacharier LB, Am J Respir Crit Care Med 2004; 170:426–432.

mean % pred. FEV1/FVC in children wih different asthma severity

90 –80 –70 –60 –50 –40 –30 –20 –10 –00

100 -

88.3%

mild intermittent

mild persistent

moderate persistent

severe persistent

86.3% 83.0% 79.8%

p<0.0001 for trend

Small airways

Peripheral airway impairment measured by oscillometry predicts loss of asthma control in

childrenShi Y., JACI, 2013;131:718-23•Impulse oscillometry (IOS) assesses airways resistance and

reactance during tidal breathing and has been increasingly used to separately quantify the degree of obstruction in the central and peripheral airways. •Because low oscillation frequencies can be transmitted more distally in the lungs compared with higher frequencies, resistance of the respiratory system at 5 Hz (R5) reflects obstruction in both the peripheral and central airways, resistance of the respiratory system at 20 Hz (R20) reflects the central airways only, and the difference between R5 and R20 (R5-20), an indicator of frequency dependence of the resistance, is an index of the peripheral airways only. •The low-frequency reactance area (AX) is the total reactance at all frequencies between 5 Hz and the resonant frequency and reflects changes in the degree of obstruction in the peripheral airways.

R20R20

R5R5

R5R5

54 children (age, 7-17 years) with controlled asthma.

Spirometric and impulse oscillometry (IOS) at baseline and at a follow-up visit 8 to 12 weeks later.


childrenShi Y., JACI, 2013;131:718-23

2 –

1 –

0

Frequency dependence of resistance (difference of R5 and resistance of the

respiratory system at 20 Hz [R5-20]

Patients who maintained

asthma control between 2 visits

Patients whose asthma became uncontrolled on

thefollow-up visit

0.7cmH2O

2cmH2O

P <0.01


childrenShi Y., JACI, 2013;131:718-23

Patients who maintained

asthma control between 2

visits

Patients whose asthma became uncontrolled on

thefollow-up visit

4.1cmH2O

13.1cmH2O

15 –

10 –

5 –

0

Reactance area at baseline

P <0.01

54 children (age, 7-17 years) with controlled asthma.

Spirometric and impulse oscillometry (IOS) at baseline and at a follow-up visit 8 to 12 weeks later.

Anamnesiquestionari

A 21 item questionnaire was administered to 343 patients with asthma and their caregivers

7 items were selected from regression analyses to comprise the C-ACT

A score ≤ 19 indicated

inadequately controlled asthma (specificity 74%, sensitivity 68%)

Development and cross-sectional validation of the Childhood Asthma Control Test.

Liu AH, J Allergy Clin Immunol. 2007;119(4):817-25.

Evaluation of association between exercise-induced bronchoconstriction and childhood asthma control test questionnaire

scores in childrenChinellatoI. Pediatr Pulmonol 2012;47:226-32

92 asthmatic children.

EIB evaluated by exercise challenge.

C-ACT score.

Of the 92 studied children only 6 (6.5%)

children had a concordance between a positive challenge test

(ΔFEV1 ≥ 13%) and a positive response to the exercise-related issue of the C-ACT

questionnaire (C-ACT total

score ≤ 19).

The two single questions showing a significant association with EIB were those focusing on nocturnal asthma.





C-ACT score.

The two single questions showing a significant association with EIB were those focusing on nocturnal asthma.





C-ACT score.

If you want to identify EIB ask for:

1) Nocturnal symptoms,2) If the child fatigues earlier than his peers during exercise.

Control levels according to the different modalities of assessment

According to pediatrician’s

assessment , 89% of patients with a C-ACT > 21 were

controlled and

85% of patients with a C-ACT < 17

not controlled

Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C-

ACT), and physician’s ratingDeschildre A. Allergy 2014;69:784

Limitations of asthma control questionnaires in the management and follow up of childhood

asthma.Carroll W, Paediatr Respir Rev. 2013;14(4):229-31.

In the presence of sensible care from compassionate and well informed doctors and nurses asthma control questionnaires will not improve outcomes for children.

A patient-focused clinical encounter supplemented with lung function measurements and occasional eNO testing has more to offer families and children than control questionnaires and their routine use in the clinic cannot berecommended on the basis of current evidence.

% children with an asthma attack in the previous year

70 –

60 –

50 –

40 –

30 –

20 –

10 –

00

56.3%

>200

60.0% 62.2%

>300 >400Blood eosinophil level

(cells/µL)

OR=1.1

OR=1.35

OR=1.65

Data from the National Health and Nutrition Examination Survey (NHANES) survey of the US general population.

Patients with asthma

identified on self-report or parental report.

Blood eosinophil count using 200, 300, or 400 cells/µL (mm3) as cutoffs.

High blood eosinophil count is associated with more frequent asthma attacks in asthma patients

Tran TN. Ann Allergy Asthma Immunol 2014;113:19-24

Nitric Oxide

FeNO and asthma treatment in children: a systematic review and meta-analysis.

Lu M, Medicine (Baltimore). 2015;94(4):e347.

6 randomized control trials that investigated the use of FeNO compared with conventional monitoring in managing asthma in children

506 subjects whose treatment was monitored using FeNO and

511 subjects who were managed using conventional methods.

no difference between the FeNO and the conventional groups in: 1) change from baseline in FEV1 2) steroid use

However, the FeNO group was associated with a lower frequency of >1 asthma exacerbation (95% CI: 0.532, 0.895).

Sex differences in measures of asthma control in adults.

On short-term (recent symptoms, asthma attacks, and albuterol use).

Long-term (asthma attacks, work days lost, and urgent-care visits and hospitalizations in the prior year).

2.0 -

1.5 -

1.0 –

0.5 –

0

1.68

SHORT-TERM

LONG-TERM

1.24

The effect of sex on asthma control from the National Asthma Survey.

Temprano J, J Allergy Clin Immunol. 2009;123:854-60.

Pay particular attention to

female patients

Yentl syndrome

aOR FOR POOR ASTHMA CONTROL IN WOMEN vs MEN


[email protected]



Achieving and maintaining asthma control in inner-city children. Scott JACI 2011;128:56

Inner-city children of low socioeconomic status have poor asthma control.

Specialty-based asthma care in mobile asthma clinics designed to reduce barriers to delivering effective asthma care (the Breathmobile Program).

7822 pediatric patients with asthma (34,339 visits).

Pre and post year data for subjects enrolled in the program for at least 1 year.

Emergency

department visits Hospitalization

s

Missed school days

≥5/yr

-00-10 –-20 –-30 –-40 –-50 –-60 –-70 –-80 –-90 –

Post program reduction in the % of

patients reporting

-66%

-84%-78%

Asthma control can be obtaned by

Using controller medications as prescribed.

Having and using an up-to-date asthma action plan available for use by all caregivers.

Using rescue medications at the child’s first symptoms of an acute exacerbation.

Having a collaborative partnership with the child’s pediatrician, including regular asthma planning visits at least every 6 months.

1) Show nonverbal attentiveness2) Give nonverbal encouragement3) Give verbal prise for things done well4) Maintain interactive conversation5) Find out underlying worries/concerns6) Give specific reassuring information7) Tailor medication schedule to family’ routine8) Reach agreement on a short-term goal9) Review the long-term therapeutic plan10) Help the patient to make decision on asthma

management

THEACHING AND COMUNICATION BEHAVIOURS

Impact of education for physicians on patient outcomes.

Clark NM, Pediatrics. 1998;101(5):831-6.

30 –

20 –

10 –

0(IPSRT) CONTROL

MINUTES SPENT FOR A VISIT

22.827.1

p=0.007

74 general practice pediatrician

Partecipated to an interactive program based on self-regulation theory (IPSRT)

Control group with no seminar

Follow-up 5 mo

Impact of education for physicians on patient outcomes.

Clark NM, Pediatrics. 1998;101(5):831-6.

Patient–provider communication strategies L Kari Hironaka, Arch Dis Child

2008;93:4281) Remove unnecessary complexities Communicate using plain language– Use plain words and keep sentence structure simple.

Avoid using jargon

Limit items discussed– Focus the discussion on the two or three most importantideas and reiterate these messages. Too much information or too many options may be overwhelming and sometimes result in decisions that are inconsistent with a patient’s values.

Repeat important points


2008;93:4282) Be specific Provide clear, specific action-oriented steps– Information should answer the question, ‘‘What do I need to do?’’

Take the patient’s perspective and consider what points remain unclear

Present the most important information through a variety of communication modalities: pictures, written and oral communication, video or interactive computer-based material Think like an educator!– Be creative and engage the learner.


2008;93:4283) Help patients to ask questionsProvide an environment conducive to learning and asking questions– Questions such as, ‘‘Do you understand?’’ may actuallyinhibit discussion. Consider instead, ‘‘I have asked you somany questions. What questions do you have for me?’’

‘‘Ask Me 3’’– Ask Me 3 is a campaign to promote health communicationby having patients ask three questions in every healthcareencounter: (1) What is my main problem? (2) What do I need to do? and (3) Why is it important for me to do this?

THE TEACH-BACK TECHNIQUE

Do not ask a patient, “do you understand?”

Instead, ask patients to explain or demonstrate how they will undertake a recommended treatment or intervention.

It the patient does not explain correctly, assume that you have not provided adequate teaching. Re-teach the information using alternate approaches.

Help patients understand: manual for clinicians B.D. Weiss 2007

Zen and the Art of Pediatric Health MaintenanceKlass P., NEJM 2012;367:103-105

Learn to be truly in the moment during the visit — to still yourself, concentrate your mind, pay attention.

Don’t let your mind rush ahead during patient encounters — have to do the prescriptions, see the next patient, get out of here and pick up my own kid, write my charts.

Look at the patient, think about the patient, pay attention to what you hear.

You shouldn’t be thinking it through later and raising the important questions — it’s all about being in the moment.

Zen and the art of health care maintenance: it’s being there in the exam room, in the moment — clearing away the noise of yourself so you can look with eyes that aren’t looking beyond the person in front of you, listen with ears that are truly hearing what is said and what is not said.

Zen and the Art of Pediatric Health MaintenanceKlass P., NEJM 2012;367:103-105

“Il potere di adesso”Tolle Eckhart

“Il dono del silenzio”Thích Nhất Hạnh

19° FORMAT Verona 12-13/05/2017

Grazie per la vostra attenzione alla storia che vi ha raccontato il mio nonno.Ciao a tutti.Mia Charlize Powell

Health & Medicine

Format 2016: how to get asthma control: from PubMed to the tricks of the trade