2015

The Year Book ofPULMONARY

DISEASE�

Editor-in-Chief

James A. Barker, MD, CPE, FACP, FCCP, FAASMVP and Medical Director, Clinical Services, University Health System; AdjunctProfessor, UT Health Science Center at San Antonio, San Antonio, Texas

2015 Year Book of Pulmonary Disease

What’s Included?Topics in the Year Book include:

ISSN: 8756-3452ISBN: 978-0-323-35553-7

Price:$180.00 USD€137.00 EUR$235.00 CAD£113.99 GBP

Save time, stay current and improve patient outcomes

The Year Book of Pulmonary Disease brings you abstracts of the articles that reported the year's breakthrough developments in pulmonary disease carefully selected from more than 500 journals worldwide.

Expert commentaries evaluate the clinical importance of each article and discuss its application to your practice.

-Asthma-Cystic Fibrosis-Chronic Obstructive Pulmonary Disease-Lung Cancer-Community-Acquired Pneumonia-Lung Transplantation -SleepDisorders-Critical Care Medicine

Click here to purchase your copy today!

Associate Editors

Shirley F. Jones, MD, FCCP, FAASMMedical Director, Scott and White Sleep Institute, Assistant Professor ofMedicine, Scott and White Healthcare/Texas A&M Health Science Center;Division of Pulmonary, Critical Care and Sleep Medicine, Temple, Texas

Janet R. Maurer, MD, MBAClinical Professor of Medicine, University of Arizona College of Medicine,Phoenix, Phoenix, Arizona

Christopher D. Spradley, MD, FACP, FCCPMedical Director, Pulmonary Hypertension Clinic, Assistant Professor ofInternal Medicine, Division of Pulmonary, Critical Careand Sleep MedicineScott & White Memorial Hospital/Texas A&M Health Science Center,Temple, Texas

Lynn T. Tanoue, MDProfessor of Medicine, Vice-Chair for Clinical Affairs, Department of InternalMedicine; Clinical Chief, Section of Pulmonary, Critical Care and SleepMedicine, Yale School of Medicine, New Haven, Connecticut

Sandra K. Willsie, DO, MAStaff Pulmonologist, KC Care Clinic, Kansas City, Missouri

iii

1 Asthma, Allergy, andCystic Fibrosis

Introduction

This year’s highlighted publications about asthma and cystic fibrosis(CF) were chosen from scores of articles, and those appearing in this chap-ter reflect investigations that we believe hold particular significance for thepracticing clinician.

Asthma remains the culprit of inordinate use healthcare resources and asignificant cause for morbidity, regardless of the age of the patient. A veryprovocative investigation published in 2014 by Raedler and colleagues1

highlighted extensive work on allergic and non-allergic asthma pheno-types. The results of this research shed light on immune-regulatory cellularmechanisms at work in childhood asthma. The potential for identificationof new pathways to provide the basis for individualized strategies forasthma prevention is promising and appears not too far awaydexciting!

Avery practical and clinically important manuscript chosen for highlight-ing in the 2015 Review includes “Management of acute loss of asthmacontrol in the yellow zone: a practice parameter,”2 which represents an evi-dence-based practice parameter calling for focus on the yellow zone by prac-titioners and education of patients on how to manage this zone. Theintervention to be recommended for patients who reach the yellow zonewill depend upon what type of dosing the subject is taking with regard toinhaled corticosteroid (ICS), eg, scheduled dosing of ICS alone; using ICSwith short-acting, quick-onset reliever; using ICS with long-acting beta ago-nist). Due to the current paucity of research on how best to handle the yellowzone, and the fact that intervention in the yellow zone has the potential toprevent morbidity (emergency department visits, missed school, hospitaliza-tion), it seems high time that a practice parameter has been written. Kudos tothe three organizations involved: American College of Allergy, Asthma, andImmunology; Joint Council on Allergy, Asthma, and Immunology; Ameri-can Academy of Allergy, Asthma, and Immunology! It is my strong recom-mendation that all healthcare providers caring for asthmatics take a carefullook at this practice parameter and implement it immediately!

Several studies of asthma therapeutics were published this year, includinga randomized, double-blind, placebo-control, parallel group, multi-centerstudy of benralizumab (B), an anti-interleukin 5 receptor alpha monoclonal

1

antibody.3 B reduced asthma exacerbation rates over 12 weeks by 49%(p¼ 0.01) and exacerbations resulting in hospitalization by 60%(p¼ 0.02). Additionally, several studies were published studying a long-acting muscarinic antagonist, umeclidinium (UMEC), in asthma, bothwith and without inhaled corticosteroids (ICS).4,5 UMEC led to significantimprovements in change from baseline trough FEV1.1 UMEC was rapidlyabsorbed and showed evidence of some accumulation. In the absence ofICS, there appeared no therapeutic benefit in the asthmatics studied.5

A study published by Bergert et al,6 demonstrated successful reductionof hospital readmission rates by using a multidisciplinary asthma taskforce employing the patient-centered medical home model. This dedicatedgroup of clinicians worked for years to fine-tune their model to interveneand ensure return to the medical home for follow-up visit following hos-pitalization of children for asthma and documented successful reductionin hospital readmission rates!

SeveralCF investigations were chosen for inclusion in this 2015YEAR BOOK,including a review of gene therapy for the treatment of CF.7 As might beexpected, this represents a very complex subject due to the tremendous num-bers of known mutations that exist, and not all mutations respond to the sametherapeutic interventions. Nevertheless, there has been tremendous advance-ment in the field of genetics of CF to date. In addition, a registry-based study8

now allows us to more accurately predict longevity in patients with CF:Median survival of children born with CF in 2010 is projected to be37 years (CI, 35-39 years) for females and 40 years (CI, 39-42 years) formales, if mortality remains at 2010 levels. The CF Foundation published clin-ical care guidelines in December 2014 for the prevention ofPseudomonas aer-uginosa (PA) infection, treatment of initial PA infection, and the use ofbronchoscopy for obtaining routine airway cultures in individuals with CF.9

Finally, we hope that you enjoy reviewing this selection of publicationsas much as we enjoyed selecting them for you.

Best regards professionally,Sandra K. Willsie, DO, MA

References

1. Raedler D, Ballenberger N, Klucker E, et al. Identification of novel immune phe-notypes for allergic and nonallergic childhood asthma. J Allergy Clin Immunol.2015;135:81-91.

2. Dinakar C, Oppenheimer J, Portnoy J, et al. Management of acute loss of asthmacontrol in the yellow zone: a practice parameter. Ann Allergy Asthma Immunol.2014;113:143-159.

3. Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab,an antiinterleukin 5 receptor alpha monoclonal antibody after acute asthma. Am JEmerg Med. 2015;33:14-20.

4. Lee LA, Briggs A, Edwards LD, Yang S, Pascoe S. A randomized, three-periodcrossover study of umeclidinium as monotherapy in adult patients with asthma.Respir Med. 2015;109:63-73.

5. Lee LA, Yang S, Kerwin E, Trivedi R, Edwards LD, Pascoe S. The effect of fluti-casone furoate/umeclidinium in adult patients with asthma: a randomized, dose-ranging study. Respir Med. 2015;109:54-62.

2 / Pulmonary Disease

6. Bergert L, Patel SJ, Kimata C, Zhang G, Matthews WJ Jr. Linking patient-centeredmedical home and asthma measures reduces hospital readmission rates. Pediatrics.2014;134:e249-e256.

7. Armstrong DK, Cunningham S, Davies JC, Alton EW. Gene therapy in cystic fib-rosis. Arch Dis Child. 2014;99:465-468.

8. MacKenzie T, Gifford AH, Sabadosa KA, et al. Longevity of patients with cysticfibrosis in 2000 to 2010 and beyond: survival analysis of the cystic fibrosis foun-dation patient registry. Ann Intern Med. 2014;161:233-241.

9. Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic fibrosis foundation pul-monary guideline. Pharmacologic approaches to prevention and eradication of ini-tial Pseudomonas aeruginosa infection. Ann Am Thorac Soc. 2014;11:1640-1650.

Asthma

Trends in the age of diagnosis of childhood asthma

Radhakrishnan DK, Dell SD, Guttmann A, et al (Children’s Hosp, London,

Ontario, Canada; Hosp for Sick Children, London, Ontario, Canada; Univ of

Toronto, London, Ontario, Canada)

J Allergy Clin Immunol 134:1057-1062, 2014

Background.dThe cause of rising asthma incidence over time remainsunexplained. Examining trends in the age of diagnosis across successivebirth cohorts may offer insights into asthma etiology.

Objective.dTo examine trends in the age at asthma diagnosis and theage and proportion of children hospitalized at first asthma diagnosis inOntario, Canada.

Methods.dEight consecutive birth cohorts of children (1993-2000)were observed using administrative data from a universal health insuranceplan in Ontario, Canada (population 13 million). Trends in the need forhospitalization and age at asthma diagnosis were examined with descrip-tive and survival analyses.

Results.dThe records of 1,059,511 children were examined, of whom201,958 developed asthma in the first 8 years of life, with an averagecumulative incidence of 19.1%. Mean age at asthma diagnosis decreasedfrom 4.7 ± 1.5 years in birth year 1993 to 2.6 ± 2.0 years in birth year2000 (P < .0001), with a higher adjusted risk of asthma diagnosis (hazardratio, 6.7; 95% CI, 6.5-6.9) in the first 3 years of life for children bornafter 1996 versus children born in the period 1993 to 1995 (hazardratio, 1.4; 95% CI, 1.3-1.4). The proportion of children hospitalized atasthma diagnosis stayed stable while the age at first asthma hospitalizationdecreased over time (P < .0001).

Conclusions.dThis study demonstrates a significant increase in asthmaincidence and a decrease in the age of asthma diagnosis across multiplebirth cohorts. Changes in asthma incidence over time are primarilyexplained by variations in asthma rates in children younger than 3 years(Fig 2, Table 1).

:

This study evaluated all children born between 1993 and 2001 in the single

province ofOntario, a single-payor system, evaluating the incidence of childhood

Chapter 1eAsthma, Allergy, and Cystic Fibrosis / 3

FIGURE 2.dA, Incidence of asthma in the first 8 years of life per cohort, stratified by age at diagnosis.Total sample size: N ¼ 1,059,511 children in total and 201,958 children with asthma. aP < .0001 for sig-nificant increase in overall asthma incidence and asthma incidence in children younger than 3 years byCochrane Armitage trend test. B, Proportion of children with asthma hospitalized at diagnosis, stratifiedby age at diagnosis. Total sample size: N ¼ 201,958 children with asthma. aP < .001 for significant increaseover time in proportion of children younger than 3 years hospitalized at first asthma diagnosis. bP < .001for significant reduction over time in proportion of children 3 years or older hospitalized at first asthmadiagnosis. (Reprinted from Radhakrishnan DK, Dell SD, Guttmann A, et al. Trends in the age of diagnosisof childhood asthma. J Allergy Clin Immunol. 2014;134:1057-1062, Copyright 2014, with permissionfrom Elsevier.)

4 / Pulmonary Disease

asthma and the age at diagnosis, and observing their care, admissions, and treat-

ment over time. Table 1 shows the mean age of asthma diagnosis by birth year

cohort (1993e2000; total of 201962 cases of asthma). Themean age of diagno-

sis in 1993was 4.7 years, 1.5 and in 2000, 2.6 years 2.0 (P< .001). Fig 2 depicts

the incidence of asthma in the first 8 years of life, stratified by age of diagnosis

and the proportion of children with asthma hospitalized at the time of diagnosis.

There was a significant increase (P< .0001 in overall asthma incidence and

asthma incidence in children younger than 3 years) and a significant reduction,

over time, in the proportion of children 3 years or older hospitalized at the time

of diagnosis of asthma (P< .001). The investigators cite previous studies indi-

cating that childhood asthma that persists into adulthood is more likely to

develop before the age of 3 years1 and that this trendmay equate to a greater bur-

den for the health care system in the long run. Importantly, in this investigational

population, the increased burden of asthma among preschool children warrants

modification of health care delivery and treatments to target this youngest age

group. Future research into primary prevention of asthma in the early years fol-

lowing birth must become a priority.

S. K. Willsie, DO, MA

Reference

1. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ.Asthma and wheezing in the first six years of life. The Group Health Medical Asso-ciates. N Engl J Med. 1995;332:133-138.

Asthma: pathogenesis and novel drugs for treatment

Olin JT, Wechsler ME (Natl Jewish Health, Denver, CO)

BMJ 349:g5517, 2014

Asthma affects almost 20 million people in the United States and morethan 300 million people worldwide. Of these, 10-15% have severe asthma,which is refractory to commonly available drugs. New drugs are neededbecause those that are currently available cannot control symptoms andexacerbations in all patients and can cause adverse reactions. In the past10 years, there have been substantial advances in the understanding of

TABLE 1.dMean Age of Asthma Diagnosis by Birth Cohort

Age (y)Birth Year

1993 1994 1995 1996 1997 1998 1999 2000

Mean � SD 4.7 � 1.5 3.9 � 1.8 2.9 � 2.0 2.5 � 2.1 2.5 � 2.1 2.6 � 2.1 2.6 � 2.1 2.6* � 2.0

Total N used for analysis¼ 201,962 (asthma cases).*P < .0001 for significant reduction in mean age of asthma diagnosis over time.Reprinted from The Journal of Allergy and Clinical Immunology. Radhakrishnan DK, Dell SD, Guttmann A, et al. Trends

in the age of diagnosis of childhood asthma. J Allergy Clin Immunol. 2014;134:1057-1062, Copyright 2014, with permis-sion from Elsevier.

Chapter 1eAsthma, Allergy, and Cystic Fibrosis / 5