ELIXIR INTERNATIONAL JOURNAL

Elixir International Journal Publication January 2015

ELIXIR INTERNATIONAL JOURNAL (Available online at www.elixirpublishers.com)

Index Copernicus, Poland Value (ICV) is

5.79 in 2012 (5.09 in 2011)

January 2015 Issue


Table of Contents

S.No Title of the Article and Author(s) Issue No. Page No. Year Month

1 Emerging trends in Human Resource Management

B.N.Venugopala and R.C.Nagaraju

78 29415-29417 2015 January

2 Adverse health effects, risk perception and pesticide use

behavior

Muhammad Khan

78 29418-29422 2015 January

3 Speed analysis for QOS in ATM network – a comparison

Sanyam Agarwal, A.K. Vatsa and Sunil Kumar

78 29423-29425 2015 January

4 Simultaneous Determination of Dorzolamide hydrochloride

and Timolol maleate in ophthalmic solutions using HPLC

W.A. Shadoul, E.A. Gad Kariem, M.E. Adam and K.E.E.

Ibrahim

78 29426-29429 2015 January

5 New spectrophotometric methods for the determination of

Entacapone in bulk and pharmaceutical dosage forms

Neeha Tadipaneni and Devala Rao Garikapati

78 29430-29431 2015 January

6 Necessity of commodity markets in Indian economy

V.Sreedevi

78 29432-29434 2015 January

7 Security issues in cloud computing

Kevin Curran, Sean Carlin and Mervyn Adams

78 29435-29438 2015 January

8 Duplicate of domestic behavior in Iran’s foreign policy

arena during Khatami presidency

Reza Ekhtiari Amiri, Majid Khorshidi and Fakhreddin

Soltani

78 29439-29444 2015 January

9 Sub Threshold Source Coupled Logic based Design of Low

Power CMOS Analog Multiplexer

G.Deepika, P.Rama Krishna and K.S.Rao

78 29445-29449 2015 January

10 Anti-inflammatory activity of Spathodea campanulata P.

Beauv. leaves against Carrageenan Induced Paw Edema

M.Vijayasanthi, A.Doss and KV.Kannan

78 29450-29452 2015 January

11 Investigational study on discovery of face in versatile

circumstances through Genetic and Ant Colony

Optimization Algorithm

S. Venkatesan, R. Vijayakanth and S. Ramesh

78 29453-29458 2015 January

12 Appraise the consequence of internal marketing strategy for

competitive advantage (case study: motor pump industries)

S.Raj Kumar, J Clement Sudhahar, T.S.Venkateswaran

78 29459-29462 2015 January

13 Evaluation of the EFL Textbook “Four Corners” from the

Perspectives of Students

Masoomeh Hanafiyeh and Mansour Koosha

78 29463-29472 2015 January

14 Prime Number Generation Using Genetic Algorithm

Arpit Goel and Anubhooti Papola

78 29473-29476 2015 January

15 Study of interpolation techniques in multimedia

communication system - A review

Apurva Sinha

78 29477-29479 2015 January

16 A Survey on Space Time Block Coding in Wireless

Communication

Preeti Sureshwar and Achint Chugh

78 29480-29483 2015 January

17 An ANN based Mobile Robot Control through Voice

Command Recognition using Nepali Language

Neerparaj Rai and Bijay Rai

78 29484-29488 2015 January

18 The Magic of the Students’ Research Houses: The Effects

of the Students’ Research Houses on the Students’ Spirit

and Educational Achievements

Seyyed-Ali Madineh, Hosein Behzādnezhād, Mahnāz

Yazdekhāsti and Zohreh Farrokhtabār

78 29489-29491 2015 January

Announcement from the Editor-in-Chief

Elixir International Journal (ISSN: 2229 -712X)

Available online at www.elixirpublishers.com


Table of Contents


19 A Comparative Study an Experimental Investigation on

Performance and Emission Characteristics of Diesel Engine

Using Bio-Diesel as an Alternate Fuel

P.Lakshmanan and G.Mariammal

78 29492-29495 2015 January

20 Some aspects of energy efficient for refrigeration and air

conditioning

Abdeen Mustafa Omer

78 29496-29504 2015 January

21 Measuring Job Satisfaction in Hospitality Industry

Rosliza Md Zani, Farah Merican Isahak Merican, Shuhaimi

Samanol and Mohamad Raimi Hashim

78 29505-29508 2015 January

22 Initial exploration of Hydrocarbon resources by Gravity

Data: A Case Study inthe South of Qom Province, Iran

Payam Salimi and Asghar Teymoorian Motlagh

78 29509-29512 2015 January

23 The Impact of Frequent Exposure to Authentic Audio

Visual Material on Enhancement of Iranian EFL Learners’

Listening Comprehension Ability

Touran Ahour and Samira Rahbar

78 29513-29517 2015 January

24 Textbook Evaluation: ELT Teachers` Perspectives on

"Learning to Read English for Pre-University Students"

Mehrdad Rezaeian, Mostafa Zamanian

78 29518-29525 2015 January

25 Innovation of Mechanical Machinery in Medieval

Centuries, Part V: Balances and Astrolabes

Galal A. Hassaan

78 29526-29534 2015 January

26 Aromoncrypt: A Technique to Optimize the Security by

Ensuring the Confidentiality of Outsourced Data in Cloud

Storage

L. Arockiam and S. Monikandan

78 29535-29539 2015 January

27 User group model for mobile social based networks

Amol S Nalge and S.R. Durugkar

78 29540-29543 2015 January

28 A review on heat transfer enhancement in NEILS for Solar

Applications

Hridesh Sreedharan and Jose K Jacob

78 29544-29548 2015 January

29 Changes induced by meloidogyne incognita on nutrient

content of mentha (mentha arvensis)

S. K. Thakur

78 29549-29551 2015 January

30 Decomposition of a weaker form of fuzzy continuity

M. Jeyaraman, J. Rajalakshmi and R.Muthuraj

78 29552-29556 2015 January

31 Performance analysis of Image Compression using Multiple

Description Coding based on Set Partitioning In

Hierarchical Tree

Shweta Gaur, Mukesh kumar, A.K. Jaiswal and Rohini

Saxena

78 29557-29560 2015 January

32 Salt tolerance mechanism of sugarcane and management

practices under sodic soil

S.Manjula, A.Vadivel and M.Jayalakshmi

78 29561-29562 2015 January

33 Thermal designing of shell & tube heat exchanger: a review

Sigimon.N.B, Jose K Jacob and A.Surendran

78 29563-29569 2015 January

34 Modified analysis of Rathore – Bhattacharya analog

multiplier

K.C.Selvam

78 29570-29571 2015 January

35 Phase Sensitive Detector using Quadrature Oscillator

K.C.Selvam

78 29572-29574 2015 January

36 Modeling the Available Production of Wind Power Plants

Hossein Reza Bayatpour, Mohammad Tajpour, Behrouz

Moarref

78 29575-29580 2015 January

37 The Effect of Post-writing Activities on the Writing 78 29581-29585 2015 January





Table of Contents


Proficiency of Iranian EFL Learners

Mehdi Bagheri

38 Determinants of Stock Price Variability

Hafiza Sidra Khurshid, Muhammad Omar and Aqsa Noreen

78 29586-29589 2015 January

39 Corporate Social Responsibility: A Constitutional

Discourse An Alternative Argument for Corporate Social

responsibility

Girjesh Shukla

78 29590-29596 2015 January

40 Financial analysis of selected Indian gas distribution

companies during 2009-2013

Rohit Bansal

78 29597-29605 2015 January

41 Armenian Theory of Special Relativity

Robert Nazaryan and Haik Nazaryan

78 29606-29617 2015 January

42 The Effect of Irrigation Methods and Operational

Pressuresin Water Use Efficiency and Productivity of

Maize (Zeamays L.)

Abdulrazzak A. Jasim Alzubaidi Zena Allawi Habeeb

Alrawshdie

78 29618-29621 2015 January

43 The Contrastive Pragmatic Analysis of Refusal Speech

Acts in English and Persian Fairy Tales: A Natural

Semantic Meta-Language (NSM) Approach

Babak Jafari Sobhe Sadegh and Reza Biria

78 29622-29628 2015 January

44 Physicochemical monitoring, Biodiversity and Biological

monitoring of the Vit River, Bulgaria

B. S. Boyanov, D. A. Kirin and M. N. Nikolova

78 29629-29634 2015 January

45 j-QAF in empowering Muslim Malaysian national primary

school students: issues and chalenges

Mohd Azmir Mohd Nizah and Mohd Azrani bin Asran

78 29635-29637 2015 January

46 Groundwater quality parameters in naguleru sub-basin of

Guntur district, Andhra Pradesh, India

Sarathbabu. P, John Paul. K and Sankara Pitchaiah. P

78 29638-29640 2015 January

47 The Study of Events in Shahnameh tales due to the

Intellectual and Signal Aspects

Ahamad Khanlary

78 29641-29643 2015 January

48 Knowledge, attitude and practices of married male towards

contraceptive methods at Mithi, Sindh, Pakistan

Aneel Kumar, Nudrat Zeba, Khalida Naz Memon, Din

Muhammad Shaikh and Haji Khan Khoharo

78 29644-29647 2015 January

49 On the Comparative Study of Estimators in Seemingly

Unrelated Regression Equations

A. A. Adepoju and E. I. Olamide

78 29648-29653 2015 January

50 Removal Cu(II) ions from synthetic waste water by a novel

biocarbon

Swaminathan Adaikalam and Singanan Malairajan

78 29654-29656 2015 January

51 Removal Pb(II) ions from synthetic waste water by

biocarbon of Ocimum sanctum (Lamiaceae)

Swaminathan Adaikalam and Singanan Malairajan

78 29657-29659 2015 January

52 Integrated nutrient managaement of Soybean (Glycine max

(L.) Merill) under temperate conditions of Kashmir Valley

Aziz M. A, Tahir Ali, Tahmina Mushtaq, S. Sheraz Madhi,

Tajamul Islam, S. A. Mir and A.P Rai

78 29660-29665 2015 January

53 Fuzzy Neutrosophic soft matrix model in decision making

I.R.Sumathi and I.Arockiaranii

78 29666-29673 2015 January

54 A Study to determine the Breath Holding Time, Forced

Vital Capacity(FVC), And Peak Expiratory Flow Rate

(PEFR) among patients with Bronchial Asthma at Selected

78 29674-29676 2015 January





Table of Contents


Hospital, Chennai

M.Malarvizhi, B.Hariprasad, M.Bhavani and Prasannababy

55 Diagnosing diabetes using data mining algorithms and

artificial intelligence systems

Amir Amiri and Vahid Rafe

78 29677-29680 2015 January

56 The Impact of Organizational Change towards Employees’

Performance in the Banking Sector in Malaysia

Anantha Raj A. Arokiasamy and Stanley Yap PengLok

78 29681-29687 2015 January

57 Energy and economic analysis of broiler production under

different farm sizes

Sama Amid, Tarahom Mesri-Gundoshmian, ShahinRafiee

and Gholamhossein Shahgoli

78 29688-29693 2015 January

58 A mathematical model by using bivariate normal

distribution for changes in prolactin and cortisol levels in

women undergoing in vitro fertilization and embryo

transfer treatment

S.Lakshmi and M.Goperundevi

78 29694-29698 2015 January

59 A study of “lactic acid production and recovery rate in the

copd and normal person after an exercise

Jayesh N Parmar

78 001-35 2015 January

60 Antimicrobial activity of Organic and Alcoholic extracts of

Medicinal Plants against clinically important Microbial

pathogens

V.Parivuguna and A.Doss

78 29699-29702 2015 January

61 Training the engineering students in soft skills through

J.K.Rowling’s ‘Harry potter and the philosopher’s stone’

V. Vijayalakshmi and M. Renuga

78 29703-29708 2015 January

62 Second minimum weight spanning tree in a network

S.Ismail Mohideen and B.Rajesh

78 29709-29710 2015 January

63 Detection of heavy metal resistance bioluminescence

bacteria using microplate bioassay method

P. Ranjitha and E.S. Karthy

78 29711-29715 2015 January

64 Minocycline in brain- a bench to bed side view

Vivek Sharma

78 29716-29719 2015 January

65 Proniosomes: a preferable carrier for drug delivery system

Jadupati Malakar, Prabir Kumar Datta, Sanjay Dey, Amites

Gangopadhyay and Amit Kumar Nayak

78 29720-29724 2015 January

66 Production of biodiesel from the catalytic transesterification

of Jatropha oil

S.V.A.R.Sastry and Ch.V. Ramachandra Murthy

78 29725-29726 2015 January

67 Study of subscriber satisfaction in slotted aloha and

resource allocation algorithm of GSM network

Sudhindra K R and Sridhar V

78 29727-29729 2015 January

68 Competition and marketing practices: a study of business

management institutes

Iftikar M Naikwadi, N.M .Makandar and Palanvelu

78 29730-29732 2015 January

69 Finite vocabulary text dependent speaker identification and

speech recognition

Suma Swamy, Radha.K, Shwetha Rani G, Smitha Crystal

D’Almeda, Sunil M and K.V Ramakrishnan

78 29733-29737 2015 January

70 Economic dispatch of electric power using clone

optimization technique

Neeraj Kumar Mishra and Sulochana Wadhwani

78 29738-29741 2015 January

71 Pyruvate kinase and haemoglobin levels in breast

carcinoma patients

Ravi Babu.Birudu and M.Jagadish Naik

78 29742-29745 2015 January





Table of Contents


72 Medicinal properties of annona squamosa in theraupitic use

B.Ravi Babu and M.Jagadish Naik

78 29746-29750 2015 January

73 Hardiness and Achievement Motivation as factors of

Academic Achievement

Bansal, P and Pahwa, J

78 29751-29754 2015 January

74 Histological Effects of Smokeless Tobacco onthe

Endometrial Glands of the Orally Treated Female Swiss

Albino Rats

Syna Pervaiz Singha and Afroz Saleem Kazi

78 29755-29757 2015 January

75 Detection of UDP, TCP and ICMP anomalies on real time

traffic

Mahendra Kumar Rai and Vijay Shankar Mishra

78 29758-29760 2015 January

76 A deterministic model for the transmission dynamics of

infectious diseases among infants

Binuyo, Adeyemi O

78 29761-29764 2015 January

77 Solid-phase extraction Citalopram by C18 modified carbon

nanotubes in water and Human Plasma samples and

determination of using HPLC

Ali Moghimi, Masome Mokhtari, Ali Parsa and Majid

Abdouss

78 29765-29768 2015 January

78 The Reliability of "Learning Environment Preferences"

Inventory in the Malaysian Context

Norzaliza Alis, Wan Marzuki Wan Jaafar and Ahmad Fauzi

Mohd Ayob

78 29769-29772 2015 January

79 Carbon Nanospheres synthesis bypyrolysis ofcrude oil and

optimization of parameters growthby response surface

methodology (RSM)

Boufades Djamila, Doumanji Loutfi, Moussiden Anissa,

BenmebroukaHafsa, Hamada Boudjema

78 29773-29779 2015 January

80 Structure and communicative teaching method of

innovation and its application

Yingling Gu

78 29780-29782 2015 January

81 Element-free Galerkin method with wavelet basis and its

application in electromagnetic field

Xia Mao-Hui and Ren Wei-He

78 29783-29786 2015 January

82 Formulation development of salicylic acid derma sticks for

external applications

Purushotham Rao, Kaushik Valambhia, Prabhakar Reddy,

Ravindranath, Venkateshwarlu and Prashant Sagare

78 29787-29789 2015 January

83 Formulation, evaluation & optimization of orally

disintegrating tablet of cinnarizine using sublimation

method

Bhupendra G.Prajapati, Rakesh P. Patel and Saitsh N. Patel

78 29790-29793 2015 January

84 Determination of the impact of Long-term Poultry manure

use on selected soil nutrients

Elvis Kodzo Ahiahonu, Robert C. Abaidoo and Elikem

Kwaku Ahiahiay

78 29794-29800 2015 January

85 Synthesis of some novel s-triazine derivatives and their

potential antimicrobial activity

Himanshu D. Patel, Keshav C. Patel, Kalpesh M. Mehta

and Pragnesh D. Patel

78 29811-29815 2015 January

86 An efficient ultra sound kidney image retrieval using neural

network approach

S. Manikandan and V. Rajamani

78 29816-29819 2015 January

87 A study on the efficiency of Erosion Potential Model

(EPM) using reservoir sediments

78 29820-29824 2015 January





Table of Contents


Asghar Kouhpeima, Seyed Ali Asghar Hashemi and Sadat

Feiznia

88 Molecular Identification Of Rotavirus Strains Involved In

Gastroenteritis Among Children In Federal Capital

Territory, Abuja Nigeria

F.A Kuta, A. Uba, L.Nimzing and O.M Oyawoye

78 29825-29828 2015 January

89 Relations between Metal Levels in Plant and Soil from

Waste Dumpsite within Uyo Metropolis

Akanimo N. Ekanem

78 29829-29832 2015 January

90 New Simple Stationary Solution of a Fluid Queue Driven

By an M/M/1 Queue

Sherif. I. Ammar

78 29833-29838 2015 January

91 Effect of millenium village primary school meal project on

enrollment rate and attendance of pupils in yala division,

Siaya County, Kenya

James Bill Ouda, Rose Atieno Opiyo and Paul Ogula

78 29839-29843 2015 January

92 Vector autoregressive model for monitoring carbondioxide

(co2) emission from the consumption of fossil fuels

Olayiwola. O. M, Sowola. B .O, Bisira, H. O, Aderele O. R

and Adeniyi, M. O

78 29844-29852 2015 January

93 Modelling relationship between students’ pre and post-

admission performances

Olayiwola. O. M, Bisira, H. O, Wale-Orojo. O. A, Aderele

O. R and Adeniyi, M. O

78 29853-29858 2015 January

94 Analysis of Single Phase Inverter Based Welding Machine

using PIC

Munish Vashishath

78 29859-29860 2015 January

95 Analysis of Three Phase Inverter Based Welding Machine

using PIC

Munish Vashishath

78 29861-29862 2015 January

96 New type of graph with different vertices

Mabrok EL- Ghoul, Habiba El-Zohny and Hend El- Morsy

78 29863-29871 2015 January

97 Critical Review of Success Factors of Knowledge

Management System (KMS) on Competency Building of

IT Based Organization

Bechoo Lal and Chandrahauns R. Chavan

78 29872-29876 2015 January

98 Role of Working Capital Management in Corporate

Profitability: A Case of Manufacturing Sector

Muhammad Usman, Muhammad Bilal Khan Lodhi, Asim

Mirza and Sadia Majeed

78 29877-29883 2015 January

99 Insertion opportunities of agricultural insurance in the

Republic of Armenia

M.G. Manucharyan

78 29884-29886 2015 January

100 Undergraduate students’ perception of the final year project

supervisory process: a case study at a private university in

Malaysia

Norbaizura Mohd Naim and Saroja Dhanapal

78 29892-29898 2015 January

101 In Search of Their Rights: A Womanistic Reading of

Lorraine Hansberry’s A Raisin in the Sun

Tayebe Nowrouzi

78 29899-29903 2015 January

102 Effect of integrated nutrient management on selected soil

physical properties and grain yield of maize in abakaliki,

south eastern Nigeria

Nwite, J. N. Igboji, P.O and Okonkwo G. I

78 29904-29908 2015 January

103 Evaluation of different alternative mixes for amaranthus

cruntus l. production in abakaliki south east, Nigeria

78 29909-29913 2015 January





Table of Contents


Nwite, J.N, Nwogbaga, A. C and Okonkwo, G. I

104 Inner product space in fourier approximation

Christian E. Emenonye

78 29922-29927 2015 January

105 Governance of IT in Indian Banks – An Immense Need

R. D. Kumbhar

78 29928-29931 2015 January

106 Genetic Diversity analysis in five accessions of Trigonella

based on Seed protein Electrophoresis and RAPD

Vaseem Raja, Rajdeep Kudesia

78 29932-29938 2015 January

107 Applying the integration of the Spatial Multi-Criteria

Decision Making (SMCDM) with GIS in urban land use

planning

Hadis Safarizadeh and Mahboobe Sadat Haj Mirfattah

Tabrizi

78 29939-29942 2015 January

108 Ensuring Competitive Advantage in the Nigerian Service

Sector through Performance Base Pay

Linus Vem

78 29943-29947 2015 January

109 Resource Use Efficiency in Chili Pepper Production in the

Keta Municipality of Volta Region of Ghana

Wosor, D.K and Nimoh, F

78 29948-29951 2015 January

110 The Need and Significance of Traditional Shop lot

Pavements in the Context of Town Conservation in

Malaysia

Yazid Saleh and Fauziah Che Leh

78 29952-29956 2015 January

111 Soil and foliar fertilization of mungfbean (vigna radlata (l)

wilczek) under Egyptian conditions

Ezzat .M. Abd El Lateef, M.M Tawfik, M. Hozyin, B. A.

Bakry T.A, Elewa A.A Farrag and Amany, A Bahr

78 29957-29963 2015 January

112 Synthesis, Characterization and Antimicrobial studies of

metal complexes of 1-[2’-Chloro-5’-Sulphophenyl]-3-

Methyl -4-Azo – [2”-Carboxy-5”-Sulphonic acid]-5-

Pyrazolone and Their Transition Metal Chelates

K. C. Desai and N. S. Indorwala

78 29964-29967 2015 January

113 An Overview on the Environmental Management and

Policy in Nigeria

Aminu Muhammad Fagge and Adamu Mustapha

78 29968-29977 2015 January

114 Both Ended Sorting Algorithm & Performance Comparison

with Existing Algorithm

Anuradha Brijwal, Arpit Goel, Anubhooti Papola and

Jitendra Kumar Gupta

78 29978-29982 2015 January

115 A comparison of motor development of 7- and 10-year-old

monozygotic, dizygotic twins and singletons in

Kermanshah City

Azita Haidari, Mohammad Jalilvand and Mehdi

Rouzbahani

78 29983-29986 2015 January

116 Sports accident in children: a rare cause of traumatic hip

dislocation

R.EL Zanati, A.Berrichi, H.Aitbenali, M.Irrazi, M.Boufetal,

A.Rhanim, M.Mahfoud, M.S.Berrada, C.Cuny and M.El

Yaacoubi

78 29987-29988 2015 January

117 Analysis of 238U, 235U, 137Cs AND 133Xe in soils from

two campuses in university of douala-cameroon

M.M. Ndontchueng, R. L. Njinga, E.J.M. Nguelem and A.

Simo

78 29989-29992 2015 January

118 Expression of the costimulatory molecules cd80, c86 and

MHC ii in eosinophil, during the peak of eosinophilia in the

syndrome larvas migrans

78 29993-29998 2015 January





Table of Contents


Joice Margareth de Almeida Rodolpho, Sandra Regina

Pereira de Oliveira, Laís Cristina de Souza Naiara Naiana

Dejani, Débora Meira Neris, Ricardo de Oliveira Correia

119 A Comparative Analysis Of Online Newsoaper Articles

Ghaffar Khamahani

78 29999-30003 2015 January

120 Evolution of Dual Containment Policy (the policy of

Clinton’s administration - Clinton’s Doctrine) in the

Persian Gulf

Seyed Mohsen Mirhosseini

78 30025-30030 2015 January

121 New Generation in Contemporary Iranian Architecture with

Reference to Political Approaches (1980 - 2013)

Amene Doroodgar, Mohammadjavad Mahdavinejad and

Ali Sheikhmehdi

78 30031-30038 2015 January

122 An investigation into senior high school three (shs3)

physics students understanding of measurement uncertainty

of length and time of scientitfic measurement in the volta

region of Ghana

Eliot Kosi Kumassah, Joseph Ghartey Ampiah and Adjei

Eugene

78 30039-30051 2015 January

123 Thermodynamic of Adsorption: Studying the effect of

temperature on adsorption of the metal ions from aqueous

Solutions using Non-conventional adsorbents

Okon Okon and Aniekememe-Abasi Israel

78 30052-30056 2015 January

124 Biologically Active Quercetin from Onion and its Effect on

Health

Kok Fook Seng, Bazlul MobinSiddique, Ida

IdayuMuhamad, Lee Chew Tin, Firdausi Razali,

Shahrulzaman Shaharuddin

78 30057-30063 2015 January

125 Education and ICT through the Lenses of Constructivism

Mostafa KhoshKholgh Sani, Azidah Abu Ziden and

Sakineh Younesi Marzoudi

78 30064-30066 2015 January

126 Comparison between simulators involved in Cloud

Computing and intensifying security of these software’s via

Kalman Scalar Filtering

Masoud Ale Seyyedan

78 30067-30072 2015 January

127 Making comparison between security providers in Cloud

Computing and present innovative secure scheme based on

Hybrid Kalman Filtering

Masoud Ale Seyyedan

78 30073-30076 2015 January

128 Using of fixed-interval smoother in cloud computing for

preventing of permeability and malicious actions

Masoud Ale Seyyedan

78 30077-30081 2015 January

129 Utilizing of Ensemble Kalman Filtering for preventing

presence of wrecking and destructives from cloud platforms

Masoud Ale Seyyedan

78 30082-30087 2015 January

130 Assessment of Vitellaria paradoxa population under

different land use types in Northern Ghana

Damian Tom-Dery, Danial Sakyi and Hypolite Bayor

78 30088-30096 2015 January




1

A STUDY OF LACTIC ACID PRODUCTION AND RECOVERY RATE

IN THE COPD AND NORMAL PERSON AFTER AN EXERCISE

Authors Name

Dr.Jayesh N Parmar

I/C Principal, Government Physiotherapy College, Jamnagar, Gujarat, India.

Dr.R.D.Jani

Professor, MP Shah Government Medical College, Physiology Department,

Jamnagar, Gujarat, India.

Dr.F.D.Ghanchi

Professor, MP Shah Government Medical College, Pulmonary Medicine

Department, Jamnagar, Gujarat, India.

Elixir Thesis Physiotherapy 78TP1 (2015) 1-35

Thesis Publications – Physiotherapy

Available online at www.elixirpublishers.com (Elixir International Journal)

Elixir International Journal Current Index Copernicus, Poland Value (ICV) is 5.79 in 2012

Elixir International Journal Thesis Publication January 2015

Tele:

E-mail addresses: [email protected]

© 2015 Elixir All rights reserved

ARTICLE INFO

Article h istory: Received: 5 January 2015;

Published: 8 January 2015;

2

ABBREVIATION

COPD Chronic Obstructive Pulmonary Diseases

� OBLA Onset Of Blood Lactate Accumulation

� FEV1 Forced Expiratory Volume In 1 Second

� FVC Forced Vital Capacity

� PEFR Peak Expiratory Flow Rate

� CB Chronic Bronchitis

� CAL Chronic Airflow Limitation

� COLD Chronic Obstructive Lung Disease

� CO2 Carbon dioxide

� P CO2 Partial Pressure Of Carbon Dioxide

� O2 Oxygen

� GOLD Global Initiative for Chronic Obstructive Lung

Disease

� SaO2 Saturation Of Oxygen

� SBP Systolic Blood Pressure

� DBP Diastolic Blood Pressure

� HR Heart Rate

� HRR Heart Rate At Rest

� HR1 Heart Rate Immediately After Exercise

� RR Respiratory Rate

� RRR Respiratory Rate At Rest

� BLA Blood Lactate

� BLAR Blood Lactate At Rest

� BLA1 Blood Lactate Immediately After Exercise

� BLA2 Blood Lactate After 15 Minutes Of Exercise

� BLA3 Blood Lactate After 30 Minutes Of Exercise

� SaO21 Saturation Of Oxygen Immediately After Exercise

� I.H.D. Ischemic Heart Disease

� L+

Lactate Plus

� Gm Grams

� L Liter

� CS Citrate synthase

� HADH 3-hydroxyacyl CoA dehydrogenase

3

� NADH Nicotinamide Adenine Dinucleotide

� LDH Lactate Dehydrogenase

� ATP Adenosine triphosphate

� PFT Pulmonary Function Test

� PH

� CF Cystic Fibrosis

� AECOPD Acute Exacerbation of COPD

� BMRC British Medical Research Council

� ATS American Thoracic Society

� LVRS Lung Volume Reduction Surgery

� TCA Tricarboxylic Acid Cycle

� VA/Q Ventilation/Perfusion

� PFK Phosphofructokinase

� PHT Pulmonary Hypertension

� PDH Pyruvate Dehydrogenase

� LT Lactate Threshold

� Mm milimole

� TUT Time Under Tension

� 6MWT Six Minute Walk Test

� PRE Perceived Rate Of Exertion

4

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) has only recently been seen as a

multi-systemic rather than a respiratory system disease (1)

It is acknowledged that the

inflammation which occurs and installs in COPD leads to remodeling of the airway, with

consequent impaired pulmonary mechanism and obstructed air flow (2)

Chronic obstructive pulmonary disease (COPD) has been variously labeled in the past

as chronic bronchitis (CB) and emphysema, chronic nonspecific respiratory disease, chronic

airway obstruction (CAO), chronic airflow limitation (CAL) and chronic obstruction lung

disease (COLD) depending upon the understanding of the path physiology and clinical

features of the syndrome of chronic cough and/or airways obstruction. It is only in the last

century that the disease has been better understood. Yet, the confusion in the terminology has

persisted till now. COPD is presently accepted as an overall umbrella term for a variety of

clinical disorders with chronic bronchitis at the one and emphysema at the other end of the

spectrum.

Globally, COPD has emerged as the major cause of morbidity and mortality expected

to become the 3rd

most leading cause of death and the 5th

leading cause of loss of ‘Disability

Adjusted Life Years’ (DALYs) as per projection of the Global Burden of Disease Study

(GBDS).The region-wise projections for the developing countries including India were even

worse. (3)

Extra pulmonary manifestations in COPD, in addition to pulmonary component, are

common. It has been observed in the ECLIPSE study that co morbidities were significantly

higher in patients with COPD than in smokers and never smokers (4).

The important co

morbidities associated with COPD are cardiovascular disorders (coronary artery disease and

chronic heart failure, hypertension), metabolic diseases (diabetes mellitus, metabolic

syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer,

cachexia, skeletal muscle weakness, anemia, depression and cognitive decline (5) (6)

.

Worldwide, COPD affects 329 million people or nearly 5% of the population. In

2011, it ranked as the fourth leading cause of death, killing over 3 million people. (7)

.The

number of deaths is projected to increase due to higher smoking rates and an aging

population in many countries. (8)

It resulted in an estimated economic cost of $2.1 trillion in

2010. (9)

It is generally known that a substantial portion of patients with chronic obstructive

pulmonary disease (COPD) develop lactic acidosis early in exercise and at very low work

rates (10) (11)

Lactic acidosis is unfavorable, since it puts additional stress on these patients’

5

limited ventilatory system during exercise. Recently, evidence has become available that a

reduced oxidative capacity of skeletal muscle correlates with the accelerated lactate (La)

response to exercise in COPD (12)

It has been described that COPD patients develop early lactic acidosis during lower

limb exercises, which enhances the ventilator output and imposes certain limits to the

exercise tolerance. (13)

EXERCISE AND LACTATE

The effect of lactate production on acidosis has been the topic in the field of exercise

physiology. The production of lactate does result in a hydrogen ion, potentially resulting in a

fall in pH. However, the hydrogen ion is quickly buffered by bicarbonate which forms an

intermediary in the blood stream which is quickly converted into water and carbon dioxide.

CO2 is transported to the lungs and exhaled to maintain acid-base status. This is the reason

for the increased respiratory rate with the accumulation of lactate in the blood. This process

can be written as chemical equation:

Lactic Acid →dissociates→ Lactate + H+

H+ + HCO3

- → H2CO3 → H2O + CO2 (CO2 is expired at the lungs to maintain pH)

The bicarbonate buffering system is extremely efficient at removing the acidifying

hydrogen ion and expelling it form the body in the form of carbon dioxide. The only

remaining by product of anaerobic metabolism is lactate.

Increasing partial pressure of CO2, PCO2, also causes an increase in [H+]. During

exercise, the intramuscular lactate concentration and PCO2 increase, causing an increase in

[H+], and thus a decrease in pH. Strenuous anaerobic exercise causes a lowering of pH and

pain, called acidosis.

The by-product of anaerobic glycolysis, lactate, has traditionally been thought to be

detrimental to muscle function. However, this appears likely only when lactate levels are very

high. Elevated lactate levels are only one of many changes that occur within and around

muscle cells during intense exercise that can lead to fatigue. Fatigue, that is muscular failure,

is a complex subject. Elevated muscle and blood lactate concentrations are a natural

consequence of any physical exertion. The effectiveness of anaerobic activity can be

improved through training. (14) (15)

� At slightly higher exercise intensity than lactate threshold a second increase in lactate

accumulation can be seen and is often referred to as the onset of blood lactate accumulation

or OBLA. OBLA generally occurs when the concentration of blood lactate reaches about

4mmol/L (16)

6

Owing to its major and better recognized burden from both individual and societal

perspectives, chronic obstructive pulmonary disease (COPD) is an area of intensive

epidemiological, fundamental and clinical research, leading to the publication of more than

10,000 papers each year in the Pub Med database. Among these, many report important

advances in the understanding of and care for COPD. Epidemiological aspects are the topic

of another manuscript in this issue of the European Respiratory Review. (17)

Patients with COPD have generally limited exercise capacity because of the reduced

ventilatory capacity. During a progressive exercise test, generally a patient with COPD will

reach his maximum work rate earlier and be unable to continue exercise.

Most often, treatment of the dyspnoea of patients with COPD is designed to improve

pulmonary mechanics by the use of medicine and control or reduce the chances of infection.

However, reduction of the metabolic acidosis during the exercise by exercise training is also

an important approach to reduce the ventilatory drive and ultimately exertional dyspnoea and

improve the exercise capacity of a patient. (11)

In patients with COPD strength and endurance exercise capacity are impaired. (18) (19)

Exercise capacity may be affected by many factors such as ventilator limitation, dynamic

hyperinflation and diminished oxygen uptake in the lung. (20)

In addition, impaired exercise

capacity could be caused by factors outside the lung, such as early lactate production, (10) (21)

(22) muscle dysfunction1 and cardiovascular deconditioning (e.g. higher heart rate and lower

stroke volume during exercise) (23) (24)

which may at least be partially induced by sedentary

lifestyle due to dyspnea. (25)

In so many study it is shown that early lactate is the one of the factor for the exercise

limitation in the COPD patients but how early it starts accumulating in the COPD patients

compared to normal individual and how fast it is eliminated by CO2 production is also

important as this will determine the duration of exercise so this study is mainly to compare

the rate of production and recovery of lactate in the COPD and in normal individual after an

exercise.

OVERVIEW AND DEFINITIONS

The term chronic obstructive pulmonary disease, abbreviated COPD, or sometimes

COLD (chronic obstructive lung disease), refers to a disease state characterized by the

presence of airflow obstruction resulting from chronic bronchitis or emphysema. As defined

in the recent American Thoracic Society guidelines statement regarding COPD” COLD

(chronic obstructive lung disease) is a treatable disease state characterized by airflow

limitation that is not fully reversible. The airflow limitation is usually progressive and

7

associated with an abnormal inflammatory response of the lungs to noxious particles or

gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also

produces significant systemic consequence.”

Similarly, the recent Global Initiative for Chronic Obstructive Lung Disease (GOLD)

defines as “a disease state characterized by airflow limitation that is not fully reversible, is

abnormal inflammatory response of the lungs to noxious particles or gases” (26)

ETIOLOGY

Tobacco smoking is the most common cause of COPD, with a number of other factors

such as air pollution and genetics playing a smaller role. (27)

In our country, bidi smoking is

an important factor in addition to cigarette smoking that causes COPD (28)

.

It also appears that outdoor air pollutants are significant environmental triggers for

AECOPD and chronic exposure to the traffic exposure affects the respiratory health

conditions, from increasing symptoms to emergency department visits, hospital admissions

and even mortality. Improving ambient air pollution and decreasing indoor biomass

combustion exposure by improving home ventilation appear to be effective interventions that

could substantially benefit the health of the general public. (29) (30)

PREVALENCE OF COPD GLOBALLU AND IN INDIA

The prevalence and morbidity data greatly underestimate the total burden of COPD

because the disease is usually not diagnosed until it is clinically apparent and moderately

advanced. (31)

Globally, as of 2010, COPD affected approximately 329 million people (4.8% of the

population) and is slightly more common in men than women (32)

this is as compared to

64 million being affected in 2004. (33)

By 2020, COPD is predicted to be the third leading cause of death and fifth leading

cause of chronic disability worldwide. (34)

The current prevalence of COPD in India is unclear because of variation in study

design and lack of adherence to strict protocol of the definition of COPD. (35)

SYMPTOMS

The characteristic symptoms of COPD are chronic and progressive dyspnoea, cough

and sputum production that can be variable from day to day (36)

. Chronic cough and sputum

production may precede the development of airflow limitation by many years. Conversely

significant airflow limitation may develop without chronic cough and sputum production.

8

CLASSIFICATION OF SEVERITY OF COPD

The global initiative for chronic obstructive lung disease (GOLD) has proposed a

universal guideline for the classification of COPD on the basis of both spirometry and

clinical symptoms to define stage of the disease. (37)

Universal Guideline for the Classification of Disease

PREDICTED FEV1/FVC FEV1

MILD COPD <70% >80%

MODERATE COPD <70% <50% to 80%

SEVERE COPD <70% <30%

PATHOPHYSIOLOGY OF COPD

COPD comprises pathological changes in four different compartments of the lungs

(central airways, peripheral airways, lung parenchyma and pulmonary vasculature), which are

variably present in individuals with the disease (31)

The path physiology of chronic obstructive pulmonary disease (COPD) is complex

and can be attributed to multiple components: mucociliary dysfunction, airway inflammation

and structural changes, all contributing to the development of airflow limitation, as well as an

important systemic component. (38)

PULMONARY HYPERTENSION:

P.H.T may develop late in the course of COPD and is due mainly to hypoxic vaso

constriction of small pulmonary arteries eventually resulting in structural changes that

include intimal hyperplasia and later smooth muscle hypertrophy/hyperplasia. Progressive

pulmonary hypertension may lead to right ventricular hypertrophy and eventually right side

cardiac failure.

EXACERBATIONS:

An exacerbation of respiratory symptoms often occurs in patients with COPD

triggered by infection with bacteria or viruses, environmental pollutants or unknown factors.

During this period there is more hyperinflation which leads to increased dyspnoea at the end.

SYSTEMIC FEATURES:

It is increasingly recognized that many patients with COPD have comorbities that

have a major impact on quality of life and survival. Airflow limitation and particularly

hyperinflation affect cardiac function and gas exchange. Inflammatory mediators in the

circulation may contribute to skeletal muscle wasting and cachexia and may initiate or

worsen comorbities such as I.H.D., Heart failure, osteoporosis, normocytic anemia, diabetes,

metabolic syndrome and depression.

9

Study show that the earliest manifestation of chronic obstructive pulmonary disease

(COPD) is an increase in residual volume suggesting that the natural history of COPD is a

progressive increase in gas trapping with a decreasing vital capacity (VC). The reduction in

VC forces the forced expiratory volume in 1 s to decline with it. This is aggravated by rapid

shallow breathing leading to dynamic hyperinflation. (39) (40) (41) (42)

MANAGEMENT OF COPD

An effective COPD management plan includes four components: (1) assess and

monitor disease; (2) reduce risk factors; (3) manage stable COPD; (4) manage exacerbations.

The goals of effective COPD management are to: (43)

• Prevent disease progression

• Relieve symptoms

• Improve exercise tolerance

• Improve health status

• Prevent and treat complications

• Prevent and treat exacerbations

• Reduce mortality

Appropriate diagnosis and management (from a pharmacologic and nonpharmacologic

perspective) of COPD and its associated comorbidities are important to ensure optimal

patient care. An evolving understanding of COPD as a multimorbid disease that affects an

aging population, rather than just a lung-specific disease, necessitates an integrated,

tailored disease-management approach to improve prognoses and reduce costs. (44)

PHARMACOLOGICAL THERAPY IN STABLE COPD:

Pharmacological therapy or drug which is used in the management of COPD is to reduce

the different symptoms which is associated with the COPD. The following group of the drug

is used

1. BRONCHODILATOR:

This medication is given as and when it is needed. It improves the FEV1 or other spirometry

values by altering the tone of the smooth muscle. This drug widens the airways so it easy the

expiration and so it improves the hyperinflation of the lung during the exercise and rest

2. ANTICHOLINERGICS :

The most important action of the anticholinergic drug on COPD is it block the effects of

acetylcholine on muscarinic receptors and modify the transmission at the pre-ganglionic

junction

10

3. METHYLXANTHINE:

Controversy remains about the exact effects of this drug as it has been reported to

have a range of non-bronchodilator action. Change in the inspiratory muscle function has

been reported by theophyline.

4. CORTICOSTEROIDS: It improves the symptoms, lung function and quality of life and

reduces the frequency of exacerbations in patients of COPD.

5. ORAL CORTICOSTEROIDS:

The details of corticosteroids are given below in table.

NON-PHARMACOLOGICAL THERAPY IN COPD

• SMOKING CESSATION

• PULMONARY REHABILITATION:

American Thoracic Society defined pulmonary rehabilitation as “a multidisciplinary

programme of care for patients with chronic respiratory impairment that is individually

tailored and designed to optimize physical and social performance and autonomy”

Pulmonary rehabilitation comprises a variety of interventions grouped into three main

categories: Exercise training, education, and psychological support. Typically, patients

participate in a programme of exercise rehabilitation 2–3 times a week for 6–12 weeks, at the

same time being encouraged to incorporate breathing and stretching exercises as part of their

daily routine. The physiological rationale for pulmonary rehabilitation in COPD is primarily

based on its effect on peripheral muscle dysfunction. A recent meta-analysis demonstrated

that pulmonary rehabilitation is effective in reducing dyspnoea and fatigue as well as

improving patients’ sense of control (mastery) over their condition. Without compliance with

a maintenance programme these improvements will diminish with time. The value of various

components of rehabilitation, programme length, the required degree of supervision, the

intensity of training and the best approach to maintaining programme adherence represent

issues that remain to be explored. (45) (46) (47) (48) (49) (50)

• RELAXATION

Premature expiratory flow limitation is naturally countered by pursed lip breathing in

some people, while hyperventilation may also be a component of exacerbation or episodes of

breathlessness for these reasons it has been popular to include relaxation exercises or

breathing retraining in rehabilitation classes. (45)

• NON INVASIVE VENTILATION

• LONG TERM OXYGEN THERAPY

11

• LUNG VOLUME REDUCTION SURGERY

• NUTRIOTIONAL SUPPLEMENTS

• VACCINATION

Several viruses and bacteria play a role in the exacerbation in the COPD which leads

to morbidity so it is recommended that health care professionals should use the vaccination

for the COPD patients against influenza, pneumococcal, pertusis. (51) (52)

.

The managements of COPD are not only done by chest physician but it includes many

other health care professionals like medical practitioners, nursing staff, respiratory therapist

and patient as well. (53)

LACTATE: NORMAL VALUE AND UNIT

The units of measurement of lactate vary between laboratories. Some use milligrams

per deciliter (mg.dl-1

), whereas others use milimoles per liter (mmol.l-1

) conversion between

these units is based on knowing that the molecular weight of lactic acid is 90, hence

mg.dl/L= mmol.l-1

*9

or

Mmol/L= mg.dl-1

*0.111

The normal reference value for blood lactate at rest is 5-20 mg.dl-1

Or 0.5 to 2.2 mmol/L (54)

LACTATE PRODUCTION

Before we understand that how lactate is produced it is necessary to understand the

normal metabolic pathway of the energy system in human body which is very well shown

here in diagram.

The citric acid cycle — also known as the tricarboxylic acid cycle (TCA cycle), or the

Krebs cycle,is a series of chemical reactions used by all aerobic organisms to generate energy

through the oxidation of acetate derived from carbohydrates, fats and proteins into carbon

dioxide and chemical energy in the form of adenosine triphosphate (ATP). In addition, the

cycle provides precursors of certain amino acids as well as the reducing agent NADH that is

used in numerous other biochemical reactions. Its central importance to many biochemical

pathways suggests that it was one of the earliest established components of cellular

metabolism and may have originated abiogenically.

The name of this metabolic pathway is derived from citric acid (a type of

Tricarboxylic acid) that is consumed and then regenerated by this sequence of reactions to

complete the cycle. In addition, the cycle consumes acetate (in the form of acetyl-CoA) and

12

water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct. The

NADH generated by the TCA cycle is fed into the oxidative phosphorylation (electron

transport) pathway. The net result of these two closely linked pathways is the oxidation of

nutrients to produce usable chemical energy in the form of ATP.

Lactate production occurs whenever the rate of pyruvate production from glycolysis

exceeds glucose oxidation by the mitochondria. Therefore, for increased lactate production to

be important physiologically, mitochondrial glucose oxidation must decrease under

conditions known to result in increased gluconeogenesis.

Above all this process is shown in the figure below. (55)

Glycolysis,Kreb’s cycle and oxidative phosphorylation

The dissociation of lactic acid

13

The Ox-Phos Shuttle

During rest and moderate exercise, some lactate continually forms in two ways.1-

energy metabolism of red blood cells that contain no mitochondria and 2-limitations posed by

enzyme activity in muscle fibers with high glycolytic capacity. Any lactate that forms in this

manner readily oxidized for energy in neighboring muscle fibers with high oxidative capacity

or in more distant tissue such as the heart and ventilatory muscles. Consequently lactate does

not accumulate because its removal rate equals its rate of production. (16)

During intense exercise, the respiratory chain cannot keep up with the amount of

hydrogen atoms that join to form NADH. NAD+ is required to oxidize 3-

phosphoglyceraldehyde in order to maintain the production of anaerobic energy during

glycolysis. During anaerobic glycolysis, NAD+ is “freed up” when NADH combines with

pyruvate to form lactate (as mentioned above). If this did not occur, glycolysis would come to

a stop. However, lactate is continually formed even at rest and during moderate exercise. This

occurs due to metabolism in red blood cells that lack mitochondria, and limitations resulting

from the enzyme activity that occurs in muscle fibers having a high glycolytic capacity.

During power exercises such as sprinting, running, cycling when the rate of demand

for energy is high, glucose is broken down and oxidized to pyruvate, and lactate is produced

from the pyruvate faster than the tissues can remove it, so lactate concentration begins to rise.

Once the production of lactate is occurs it regenerates NAD+, which is used up in the

creation of pyruvate from glucose, and this ensures that energy production is maintained and

exercise can continue. The increased lactate produced can be removed in two ways:

• Oxidation back to pyruvate by well-oxygenated muscle cells

14

• Pyruvate is then directly used to fuel the Krebs cycle.

• Conversion to glucose via gluconeogenesis in the liver and release back into circulation;

Cori cycle. (16)

• If not released, the glucose can be used to build up the liver's glycogen stores if they are

empty.

ONSET OF BLOOD LACTATE ACCUMULATION:

During low-intensity, steady-rate exercise, blood lactate concentration does not

increase beyond normal biologic variation observed at rest. As exercise intensity increases,

blood lactate level exceed normal variation. Exercise intensity associated with a fixed blood

lactate concentration that exceeds normal resting variation denotes the LT. This often

coincides with a 2.5 milimoles (mM) value. A 4.0 mM lactate value indicates the onset of

blood lactate accumulation (OBLA). (16)

An increased blood lactate concentration is common during physiological (exercise)

and patho physiological stress (stress hyperlactataemia). In disease states, there is

overwhelming evidence that stress hyperlactataemia is a strong independent predictor of

mortality. However, the source, biochemistry, and physiology of exercise -induced and

disease-associated stress hyperlactataemia are controversial. The dominant paradigm suggests

that an increased lactate concentration is secondary to anaerobic glycolysis induced by tissue

hypo perfusion, hypoxia, or both. (56)

The normal plasma lactate concentration is 0.3–1.3

mmol litre_1. Considered once as a special investigation, it is increasingly measured

automatically with the blood gas analysis. Plasma concentrations represent a balance between

lactate production and lactate metabolism. In humans, lactate exists in the levorotatory

isoform. Normal lactate production Glycolysis in the cytoplasm produces the intermediate

metabolite pyruvate (Fig. 1). Under aerobic conditions, pyruvate is converted to acetyl CoA

to enter the Kreb’s cycle. Under anaerobic conditions, pyruvate is converted by lactate

dehydrogenase (LDH) to lactic acid. In aqueous solutions, lactic acid dissociates almost

completely to lactate and Hþ (pKa at 7.4 ¼ 3.9) (Fig. 2). Consequently, the terms lactic acid

and lactate are used somewhat interchangeably. Lactate is buffered in plasma by NaHCO3.

Tissue sources of lactate production include erythrocytes, perivenous hepatocytes, skeletal

myocytes and skin. Basal lactate production is 0.8 mmol kg_1 h_1 (1300 mmol day_1). (55)

AIMS AND OBJECTIVES:

1. Aims of this study are to find out lactic acid production and recovery rate in the COPD

patients and in normal individual.

2. Suggest suitable modifications in exercise/stress regimes to these patients.

15

EXCLUSION AND INCLUSION CRITERIA:

1. Inclusion criteria :

• Subjects willing to participate in the study

• Age between 40-80

• Patients with C.O.P.D

2. Exclusion criteria :

• Subjects who have acute attack of dyspnoea or any respiratory infection within last 3-4

weeks

• Subjects who does regular exercise.

• SpO2 is lower than 85%.

16

METHODS:

The present study was carried out in Shri Guru Gobindsinghji Hospital, Jamnagar

with the basic aim of finding any difference between the rate of production and recovery in

the COPD and in normal individual.

17 Stable patient who met the clinical diagnosis from the department of chest and

respiratory diseases GGH, Jamnagar were recruited from GGH and the 17 normal individual

matched with age were recruited from the physiotherapy department and other department for

the measurement of lactate test.

Full approval was obtained from the MP SHAH MEDICAL COLLEGE RESEARCH

ETHICAL COMMITTEE and all participants provided informed written consent.

OUTCOME MEASURE:

The primary outcome for this study is to measure sub maximal exercise lactate

measurement and its recovery rate in patients of COPD as well as in age matched group of

normal individuals. They were recruited in consecutive disorder: They had to be considered

clinically stable without a history of any kind of infection or exacerbation and without

changes in their medication during the last 3-4 week before the commencement of the test.

We have excluded the patients whose resting SpO2 is lower than 85%.

All participants attached to the hospital, an initial baseline data were recorded. They

were introduced with the physiotherapist, disease process, pulmonary function test machine,

methods & methodology, equipment within ½ an hour. All participants were properly

instructed about PFT machine. They were instructed to sit comfortably on the chair, and

mouth piece was given to them and nose clip was kept on nose so subject may not inspire or

expired through nose. After that they were instructed to do forceful expiration followed by

forceful inspiration without any pause in between this cycle. Five to ten minutes rest was

given after the PFT test is performed

After that subjects were asked to performed incremental exercise test on an electronic

cycle ergometer. First 1 minute was only warm up with the cycling .After 1 minute of cycling

workload was increased by applying more resistance at wheel (by tightening the knob of

resistance) at every 60 seconds till the end of 5 minute. At every minute exertion level was

asked by the chart of PRE (perceived rate of exertion) which is given here, at the end of test

again the level of exertion was asked to each individual and the score was measured for each

patient and the entire normal individual in the control group. Most of the patients and normal

individuals PRE were between 13-17.

17

Lactate level was measured with the instrument known as lactometer, before the

exercise, immediately after the test, after 15 and 30 minutes of test.

The methods of using lactometer (Lactate Plus):

Lactate Plus (L+, Nova Biomedical, and USA) uses an electrochemical lactate oxidase

biosensor for the measurement of lactate in whole blood. The reliability and accuracy of

lactate plus is checked with the laboratory –based analyzer, it was good compared to the

lactate pro instrument. (57) (58)

.A blood sample of 0.7 µL is required: sample analysis time is

11 seconds .Test strips used with the L+

does not required calibration codes or specific

calibration strips. The L+ displayed good reliability and accuracy when compared to a

laboratory based analyzer. (59)

For measurement of lactate one side index finger was chosen and pulp of distal

phalanx was cleaned properly with spirit and cotton. After that lancet was used to prick the

finger and blood is taken on strip after that strip was kept in lactometer instrument area for

atleast 10-11 seconds till the value of lactate is shown on the display. Same way immediately

after exercise, after 15 and 30 minutes procedure was done on alternative finger.

Materials to be used:

� Weighing scale

� Instrument to measure lactate i.e. lactometer

� Measure tape

18

� Sphygmomanometer

� PRE scale (Perceived rate of exertion)

� Watch

� Oxymeter

� Cycle

� PFT Machine

� Pen

� Paper

PFT instrument

• Lactometer

• Lancet and its instrument

• Measure tape

• Blood lactate measurement strip

• Oxymeter

• Pen

19

CHART NO 1 AGE

COPD CONTROL

AGE 56 59.94

CHART NO 2-3 HRR AND SBP

COPD CONTROL

HRR 92.58 80.94

Systolic blood pressure

COPD CONTROL

SBP 130 127.41

56

59.94

54

55

56

57

58

59

60

61

CO

PD

CO

NT

RO

L

AGE

AGE

92.58

80.94

75

80

85

90

95

COPD CONTROL

Series1

20

CHART NO 4-5 DBP AND SPO2

COPD CONTROL

DBP 83.52 81.35

COPD CONTROL

SPO2 96.35 97.29

130

127.41

126

127

128

129

130

131

COPD CONTROL

SBP

SBP

83.52

81.35

80

80.5

81

81.5

82

82.5

83

83.5

84

COPD CONTROL

DBP

DBP

96.35

97.29

95.5

96

96.5

97

97.5

COPD CONTROL

SPO2

SPO2

21

CHART NO 6-7 RRR AND BLAR

COPD CONTROL

RRR 24.7 20.17

COPD CONTROL

BLAR 2.38 2.5

24.7

20.17

0

5

10

15

20

25

30

COPD CONTROL

RRR

RRR

2.38

2.5

2.3

2.35

2.4

2.45

2.5

2.55

COPD CONTROL

BLAR

BLAR

CHART NO 8

BLA1

BLA2

0

1

2

3

4

5

6

7

0

1

2

3

4

5

6

COPD

CHART NO 8-9 BLA1 AND BLA2

COPD CONTROL

BLA1 6.339 5.29

COPD CONTROL

BLA2 5.15 4.26

6.39

5.29

COPD CONTROL

Series1

5.15

4.26

COPD CONTROL

BLA2

BLA2

BLA3

PRODUCTION & RECOVERY RATE OF LACTATE

2.3

2.4

2.5

2.6

2.7

2.8

2.9

0

1

2

3

4

5

6

7

REST

REST

COPD 2.5

CONTROL 2.382352941

CHART NO 10 BLA3

COPD CONTROL

BLA3 2.85 2.49

CHART NO 11

PRODUCTION & RECOVERY RATE OF LACTATE

2.85

2.49

COPD CONTROL

BLA3

BLA3

REST IMMEDIAT AFTER 15 AFTER 30

COPD

CONTROL

IMMEDIAT AFTER 15 AFTER 30

6.394117647 5.15882 2.85294

2.382352941 5.294117647 4.08235 2.49412

CONTROL

AFTER 30

24

STATISTICAL ANALYSIS

COPD GROUP AND ITS DATA

No FEV1% of predicted FVC % of predicted FEV1/FVC % of predicted

AVERAGE 50.17 64.05 0.77

SD 17.16 19.38 0.06

T 8.70441E-08 0.02 3.07392E-10

SIGNIFICANT SIGNIFICANT SIGNIFICANT

NO HRR SBPR DBPR

AVERAGE 92.58 130 83.52

SD 11.41 11.95 7.52

T 0.01 0.49 0.35

SIGNIFICANT

NO BLAR BLA1 BLA2 BLA3

AVERAGE 2.5 6.39 5.15 2.85

SD 1.00 1.68 1.53 1.18

T 0.72 0.06 0.065 0.33

NO SPO2R SPO21 RRR

AVERAGE 96.35 92.47 24.70

SD 2.78 2.40 4.90

T 0.35 0.014 0.003

SIGNIFICANT SIGNIFICANT

CONTROL GROUP AND ITS DATA

NO FEV1% of predicted FVC % of predicted FEV1/FVC % of predicted

AVERAGE 95.29 81.70 1.19

SD 20.57 23.57 0.14

25

NO HRR HR1 RRR

AVERAGE 80.94 124.11 20.17

SD 14.78 9.51 2.98

NO BLAR BLA1 BLA2 BLA3

AVERAGE 2.38 5.29 4.08 2.49

SD 0.95 1.68 1.74 0.91

NO SPO2R SPO21

AVERAGE 97.29 94.82

SD 3.01 2.89

NO SBPR DBPR

AVERAGE 127.41 81.35

SD 9.91 5.77

Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

BLAR 17 40.5 2.382353 0.907794

BLA1 17 90 5.294118 2.851838

BLA2 17 69.4 4.082353 3.037794

BLA3 17 42.4 2.494118 0.845588

ANOVA

Source of Variation SS df MS F P-value F crit

Between Groups 98.64985 3 32.88328 17.20959 2.65E08 2.748191

Within Groups 122.2882 64 1.910754

Total 220.9381 67

26

RESULT

17 patients with COPD and 17 normal individual were enrolled for this study. The

detail anthropometric data and other necessary information are given in the below chart. The

criteria of GOLD classification were adopted for the COPD patients.

As per the result there is small rise in RR, SBP, and DBP in COPD patients as

compare to the normal individuals. There is no significant difference in resting blood lactate

level between COPD and normal individuals.

There is a significant difference in FEV1, FVC and FEV1/FVC between COPD and

control group. This is because COPD is an obstructive lung disorder which gives reduced

FEV1 and FEV1/FVC.

Blood lactate level at rest, immediately after exercise, after 15 and 30 minutes of

exercise are shown in the chart, which suggests that blood lactate level is increased in both

the group immediately after exercise but the increment is more in COPD group of patients

compared to the control group. Once the exercise is stopped and again blood lactate is

measured after 15 minutes, in both the group blood lactate level is reducing but still it was

higher than the baseline level, after 30 minutes of exercise the blood lactate level is almost

reached to the baseline level. The lactate level is increasing in both the group but it is

increasing more in COPD group than the control group significantly.

Heart rate immediately after an exercise is significantly more in COPD group

compared to the control group. The difference between saturation in both the group was not

significant at rest but after an exercise there is significant difference between COPD and

control group with respect to the blood saturation.

DISCUSSION

Patients with COPD may develop high ventilatory and metabolic output when they

perform simple household activity in routine base. Impaired exercise tolerance is a prominent

complaint of patients with obstructive lung disease. Unlike healthy subjects, patients with

obstructive lung disease are often limited in their exercise tolerance by the level of ventilation

they are able to sustain .Improving physical performance is an important therapeutic goal in

COPD. Recent evidence has said that muscle mitochondrial (oxidative) capacity is reduced

and that may be the reason for the exercise intolerance in this population. (60) (61) (58)

.One of

the important factor that has an effects on exercise ventilation is CO2 production which is

generated by aerobic metabolism and buffering of lactic acid, which is formed an aerobically

when oxygen demand exceeds supply to exercising muscles. (61)

27

Lactate production is a natural process and it is produced even at rest and it is

removed also, but when the production rate is increased more than removal it is accumulated,

or the removal of lactate is done by the heart, kidney, liver and non exercising muscle.

The increase in blood lactate level during the progressive exercise is the interest of

many physician, clinician, sports coaches and many researchers in today’s new era. Lactate is

the marker of peripheral muscle anaerobic metabolism and fatigue. (62).

The blood lactate

response to exercise has interested physiologists for over many years, but has more recently

become as routine a variable to measure in many exercise laboratories as is heart rate. This

rising popularity is probably due to: a) the ease of sampling and improved accuracy afforded

by recently developed micro-assay methods and/or automated lactate analyzers; and b) the

predictive and evaluative power associated with the lactate response to exercise. Several

studies suggest that the strong relationship between exercise performance and lactate-related

variables can be attributed to a reflection by lactate during exercise of not only the functional

capacity of the central circulatory apparati to transport oxygen to exercising muscles, but also

the peripheral capacity of the musculature to utilize this oxygen. (63)

The precise mechanism by which blood-lactate accumulation occurs during exercise

comprises many factors like the mass of exercising muscle, supply of oxygen to that muscle

in blood, diffusion into cells, and the efficiency of utilization by those muscle cells. (64)

The production of more lactate is one of the primary factors for the limitation of the

exercise performance in the COPD patients. Our result confirms that lactic acid production is

increased as the level and stress of exercise is increasing, but there is no significant difference

in increment level between COPD and control group with respect to the production and

recovery of the lactate.

This study has some limitation like sample size should be more, we have not

categorized the severity of COPD patients and we did not compare the lactate production and

recovery in different group of the COPD patients. We did not measure the lactate production

at the maximal cardiopulmonary exercise level as it was not the purpose of this study. In the

current study the other parameters like blood pressure and oxygen saturation is measured

only at rest and not immediately after exercise, after 15 and 30 minutes of an exercise as the

primary concern was just to measure the rate of production and recovery of lactate.

In our study the lactate production is more in the COPD patients, as in COPD patients

the oxygen supply to the body is limited or reduced as compared to the other normal

individual so during exercise as the oxygen supply is reduced the exercise shift towards the

anaerobic metabolism and the end product of anaerobic metabolism is pyruvate which

28

converts into lactate and this increases the production of lactate in COPD patients compared

to the normal individual so anaerobic metabolism break down the glycogen leads to an

accumulation of inorganic acid that is lactic acid, as lactic acid is a very strong acid it

immediately converts into lactate and hydrogen ion which indirectly causes fatigue in many

COPD patients and this is supported by the study done by Hakan westerblad in 2002. (65)

In COPD patients the respiratory rate is increased more which leads to less time for

the expiration and causes dynamic hyperinflation which is the main cause of respiratory

discomfort and exercise limitation. (66)

Katz and Sahlin (67)

had collected data and postulates that lactate production is O2

dependent .In fact they said that when O2 supply is less or limited then mitochondrial

respiration is begin by increase in ATP and Pi (inorganic phosphate) and the reduced form of

NADH (nicotinamide adenine dinucleotide).This favors the stimulation of glycolysis, which

will increases cytosolic NADH formation which will shift the lactate dehydrogenase (LDH)

equilibrium toward increase lactate production. They propose that oxygen supply plays the

most important factor in lactate production.

In 1996 F Maltais and et al done a study on COPD subjects and each subject

performed a stepwise exercise test on an ergo cycle up to their maximum limit and they

concluded that lactic acid rises steeply in COPD group and they said that the activity of the

oxidative enzymes (citrate synthase CS, and 3-hydroxyacyl CoA dehydrogenase HADH) was

significantly lower in COPD than in control group so this study also supports our study

results. (12)

F Maltais , A A Simard and et al in 1996 suggested that in COPD group compared to

the normal group, the increment in lactate production is steeper in COPD group, they said

that reason for this is the activity of the oxidative enzymes was significantly lower in COPD

groups than the control subjects. They have also found no difference in glycolytic enzymes.

They concluded that oxidative capacity of the skeletal muscle is reduced, and increase in

arterial lactate during exercise is excessive, and these both results are interrelated. (12)

In our study the increase in heart rate, respiratory rate, and systolic blood pressure is the

response of exercise in both the group. But resting heart rate and respiratory rate in COPD

group is significantly higher than the control group. The reason for this is that the impairment

in COPD brings to the pulmonary mechanism which can leads to the decrease venous return

and ultimately leads to increase heart rate at rest, and because of this there is higher blood

pressure at rest compared to the normal individuals. In this way COPD can affect the heart

29

rate at rest also and this is a very important factor as it decreases the reserve heart rate

available for any kind of exercise/efforts. (68)

In our study results suggest that lactate is increasing in both the group significantly

when they perform sub maximal level of exercise but the increment of lactate is more in the

COPD group which suggests that COPD patient gets fatigue early and easily as lactate

production is increased more than the control group at sub maximal exercise level, this is

very interesting as well as important as our routine day to day activity involves sub maximal

exercise and that might be the reason that COPD patient either don’t perform the routine

activity or if they perform these activity they gets fatigue very easily and which turns them

into avoidance of these activity which deteriorates their functional ability and capacity to

perform the routine task.

The respiratory rate is more at rest in the COPD group than the control group,

because the hydrogen ion which is produced by the dissociation of the lactic acid into lactate

and hydrogen ion with the help of bicarbonate and converts to produce CO2 and this increases

the load onto patient. Moreover the hydrogen ion itself is the stimulus for the ventilatory

drive .Both the increased in CO2 generated by buffering and the respiratory stimulation by

the hydrogen ion are perceived by the patient as breathing stimuli and which increases the

respiratory rate. (11)

The occurrence of metabolic acidosis in patients with COPD during exercise may be

crucial for the designing the proper rehabilitation protocol. For example in patents in which

develop the metabolic acidosis, exercise training has the some potential to improve exercise

tolerance. Reduction of metabolic acidosis translates into ventilatory requirements and the

same amounts of exercise can be performed with less ventilation which also reduces the

dyspnoea.

Immediately after an exercise there is more increment of heart rate in the COPD

group than the control group which suggests that in mild to moderate activity like in our

study (sub maximal exercise) also increment of heart rate is more in COPD group. The

explanation for this is again as like how heart rate is more in COPD group at rest, same way

the heart rate immediately after an exercise is more in COPD group. As the level of exercise

increases the oxygen and other nutrient material are more required to the working muscle and

in COPD group the oxygen supply is less because of the obstruction which is compensated by

more increment in the heart rate compared to the control group after a sub maximal exercise.

The lactate level is not significantly different in both the group at resting level. The

lactate level is increasing in both the group immediately after an exercise, 15 and 30 minutes

30

of an exercise but the level of increment is higher in COPD group compared to the control

group at the sub maximal level of exercise. We have not allowed any person from both the

group to reach at the maximal level of exercise as it was not the aim of my study. The level or

stress of the exercise was measured by the PRE at each minute of the exercise and at end of 5

minutes the PRE of both the group was somewhat hard to hard.

The reason why I have not chosen the maximal level of exercise is that in routine, day

to day activity mostly occurs in the sub maximal level of stress and what is the lactate level

during sub maximal level of an exercise.

So the finding of lactate production in patients with COPD may prove to be useful in

deciding whether to include exercise training as part of an individual’s rehabilitation

program. (11) (69)

CONCLUSION AND FURURE DIRECTIONS

The overall prevalence of COPD in India and in other countries in increasing day by

day despite profound research in COPD.

As COPD not only affects respiratory system but it also affects the other system in

our body, it is not confined only to the lungs but it is a multisystem manifestations. So it is

very important to understand the effects of exercise and its response to the COPD patients

which is done by this study with respect to the production of lactate and its recovery rate in

COPD patients.

The physiological change which is associated with the lactate production and

accumulation has significant influence on the cardiopulmonary performances. The lactate

accumulation leads to hyperventilation, altered oxygen kinetics and impaired muscle

performances in any individual. Thus it is very important to find out any early lactate

accumulation in COPD or any normal individual and accordingly some kind of intervention

can be given to reduce or to delay the lactate accumulation during exercise.

In conclusion the COPD group not only generates high concentration of blood lactate

similar to those observed in normal controls at sub maximal level of exercise but also this

occurs earlier than the normal group. The recovery rate is almost similar in both the group.

Measurement of the lactate threshold is a very useful way of assessing fitness and the

response to intervention, such as exercise training.

31

1. BR c, CG C, al MJe. The body mass index,airflow obstruction,dyspnoea and exercise

capacity index in chronic obstructive pulmonary disease. NEJM. 2004;: p. 350(10):1005-

12.

2. RA P, AS B, PMA C, CR J, SS H. Global strategy for the diagnosis,management and

prevention of chronic obstructive pulmonary disease(GOLD). Am J Respir Crit Care

Med. 2001; 163: p. 1256-1276.

3. Jindal S. COPD: The Unrecognized Epidemic in India. SUPPLEMENT TO JAPI. 2012

February; 60.

4. A A, PM C, B C, HO C, LD E, DA L. Characterisation of COPD heterogeneity in the

ECLIPSE cohort. Respir Res. 2010; 11: p. 122-136.

5. M.E.Franseen F, Rochester CL. Comorbities in patients with COPD and pulmonary

rehabilitation:do they matter? Eur Respir Rev. 2014; 23: p. 131-141.

6. P B, B B, LM F, al CCe. Link between chronic obstructive pulmonary disease and

coronary artery disease: implication for clinical practice. Respirology. 2012; 17: p. 422-

31.

7. The 10 leading cause of death in the world: World health organization; 2011.

8. CD M, d L. Projection of global mortality and burden of disease from 2002 to 2030.

PLOS Med. 2006; 3(11).

9. Lomborg , Bjorn. Global problems,local solutions:cost and benifits.: Cambridge

university press.

10. R C, A P, F I, S Z, CF D, K W. Reduction in exercise lactic acidosis and ventilation as a

result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis.

1991; 143: p. 9-18.

11. DY S, K W, RB M, R C. Metabolic acidosis during exercise in patients with COPD.

Chest. 1988; 94: p. 931-938.

12. F M, AA S, C S, J J, P D, P L. Oxidative capacity of skeletal muscle and lactic acid

kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit

Care Med. 1996; 156: p. 288-293.

13. Maltais F, Jobin J, Sullivan MJ, Bernard S. Metabolic and hemodynamic responces of

lower limb during exercise in patients with COPD. J Appl Physiol. 1998; 84: p. 1573-

1580.

32

14. Clark J. http://www.homeexercise.co. [Online].; 2013 [cited 2013. Available from:

http://www.homeexercise.co/anaerobic-training-exercise-definition/.

15. McMahon TA. Muscles, Reflexes, and Locomotion: Princeton university press; 1998.

16. McArdle , Katch WD, Katch FIa. Exercise physiology:Energy nutrition and human

performance.: Lippincott Willims and Wilkins Health; 2011.

17. C R, P G. Epidemiology of COPD. Eur Respir Rev. 2009; 18: p. 213-221.

18. A S, GB M, A S, M N, R B, al CMe. Fiber type in skeletal muscles of COPD patients

related to respiratory functions and exercise tolerance. Eur Respir J. 1997 December;

10(12).

19. F W, J J, PM S, C S, P L, al BSe. Histochemical and morphological characteristics of the

vastus lateralis muscle in patients with COPD. Med Sci Sports Exerc. 1998 October;

30(10).

20. R O. Ventilatory limitations in chronic obstructive pulmonary disease. Med Sci Sports

Exercise. 2001 July; 33(7).

21. R C. Skeletal muscle function in COPD. Chest. 2000 May; 117(5).

22. MP E, AM S, JD D, HR G, NE D, EF W. Exercise induced lactate increased in relation to

muscle substrates in patients with COPD. Am J Respir Crit Care Med. 2000 Nov; 162(5).

23. NR M. Mechanism of functional loss in patients with COPD. Respir Care. 2008

september; 53(9).

24. BL T. Disease management of COPD with pulmonary rehabilitation. Chest. 1997

December; 112(6).

25. AG A, A N, J S, E S, J P, X B. Systemic effects of COPD. Eur Respir J. 2003 Feb; 21(2).

26. Robert LW, K.Stoller J, M.Kacmarek R. Egan's Fundamentals Of Respiratory Care.

NINTH ed. Sharp B, editor.: MOSBY ELSEVIER; 2009.

27. Decramer M, Janssens W, Miravitlles M. Chronic Obstructive Pulmonary Disease.

Lancet. 2012 April; 379(9823): p. 1341-51.

28. SK J, AN A, K C, SK C. Asthma Epidemiology Study Group. A multicentric study on

epidemiology of COPD and its relationship with tobacco smoking and environmental

tobacco smoke exposure. Indian J Chest Dis Allied Sci. 2006; 48: p. 23-9.

29. KO FWS, HUI DSC. Air pollution and chronic obstructive pulmonary disease.

Respirology© 2011 Asian Pacific Society of Respirology. 2012; 17: p. 395-401.

33

30. Kan H, Heiss G, Rose KM, Whitsel E, Lurmann F, London SJ. Traffic exposure and lung

function in adults: the Atherosclerosis Risk in Communities study. Thorax. 2007; 62: p.

873–879.

31. Celli BR, MacNee W, members ac. Standards for the diagnosis and treatment of patients

with COPD:a summary of the ATS/ERS position paper. Eur Respir J 2004. 2004; 23: p.

932-946.

32. Vos PT, Flaxman AD, Naghavi M, Lozano PR, al CMe. Years lived with disability

(YLDs) for 1160 sequelae of 289 diseases and injuries 1990—2010: a systematic analysis

for the Global Burden of Disease Study 2010. Lancet. 2012 December; Volume

380(9859): p. 2163-2196.

33. Chronic obstructive pulmonary disease (COPD). Fact sheet. WHO; 2004.

34. AD L, CC M. The global burden of disease, 1990–2020. Nat Med.. 1998; 4(11): p. 1241-

1243.

35. McKaya AJ, Maheshb PA, Fordhama JZ, Majeedc A. Prevalence of COPD in India: a

systematic review. Prim Care Respir J. 2012; 21(3): p. 313-321.

36. Nicholas A Zwar , Marks GB, Hermiz O, Middleton S, Comino EJ, Hasan I, et al.

Predictors of accuracy of diagnosis of chronic obstructive. MJA. 2011 August; 195(4).

37. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis,

management and prevention of COPD(GOLD). [Online].; retrieved 2013. Available

from: http//www.goldcopd.com.

38. Rodríguez-Roisin R. The Airway Pathophysiology of COPD: Implications for Treatment.

COPD:A JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASES.

2005; 2(2): p. 253-262.

39. Macklem PT. Therapeutic implications of the pathophysiology of COPD. Eur Respir J.

2010; 35(3): p. 676-680.

40. Rabinovich RA, Vilaro J. structural and functional changes of peripheral muscles in

COPD patients. Curr Opin Pulm Med. 2010 March; 16(2): p. 123-133.

41. Fabbri LM, Luppi F, Beghe B, Rabe KF. Complex chronic comorbidities of COPD. Eur

Respir J. 2008; 31(1): p. 204-212.

42. Wouters EFM. COPD:Systemic effects of COPD. Thorax. 2002; 57: p. 1067-1070.

43. WHO. http://www.who.int/respiratory/copd/management/en/. [Online].

34

44. COPD and associated comorbidities: a review of current diagnosis and treatment.

Postgrad Med.. 2012 July; 124(4): p. 225-40.

45. Morgan MDL, Britton JR. Chronic obstructive pulmonary disease v 8:Non-

pharmacological management of COPD. Thorax. 2003; 58: p. 453–457.

46. Lacassea Y, Maltaisa F, Goldsteinb RS. Pulmonary rehabilitation: an integral part of the

long-term management of COPD. SWISS MED WKLY. 2004; 134: p. 601-605.

47. Suh Es, Mandal S, Hart N. Admission prevention in COPD:non-pharmacological

management. BMC Medicine. 2013; 11(247): p. 1-9.

48. Talang AA, Road J. Non-pharmacological management of chronic obstructive pulmonary

disease. BC Medical Journal. 2008 March; 50(2): p. 90-96.

49. E.M.Clini , N.Ambrosino. Non pharmacological treatment and relief of symptoms in

COPD. Eur Respir J. 2008; 32(1): p. 218-228.

50. MacNee W, Calverley PMA. Chronic obstructive pulmonary disease : Management.

Thorax. 2003; 58: p. 261-265.

51. Pesek R, Lockey R. Vaccination of adults with asthma and COPD. Allergy 2011. 2011;

66: p. 25-31.

52. Alfageme I, Vazquez R, Reyes N, Mun˜oz J, Ferna´ndez A, Merino MH, et al. Clinical

efficacy of anti-pneumococcal vaccination in patients with COPD. Thorax. 2006; 61: p.

189–195.

53. Kruis AL, Boland MR, Chavannes NH. BMC Pulm Med. 2013; 13: p. 17.

54. B.Cooper C, W.Storer T. Exercise testing and interpretation. 5th ed.: Cambridge

University press; 2010.

55. Phypers B, Pierce JT. Lactate physiology in health and. Anaesthesia critical care

medicine. 2006; 6(3): p. 128-132.

56. Garcia-Alvarez M, Marik PP, Bellomo PR. Stress hyperlactataemia: present

understanding and controversy. Lancet Diabetes & Endocrinology. 2013 November;

8587(13): p. 70154-2.

57. Tanner RK, Fuller KL, R.Rose ML. Evaluation of three portable blood lactate

analyser:Lactate pro,lactate scout and lactate plus. Eur J Appl Physiology. 2010

Fbbruary; 110: p. 551-559.

58. Souza GFd, Castro AA, Velloso M, Silva CR, Jardim JR. Lactic acid levels in patients

35

with COPD accomplishing unsupported arm exercises. Chrinic respiratory diseases. 2010;

7(2): p. 75-82.

59. K R, L K, R.Rose , L M. Evaluation of three portable blood lactate analyser:Lactate

Pro,Lactate Scout and Lactate Plus. Eur J Applied Physiology. 2010; 109: p. 551-559.

60. Calvert LD, Shelley R, Singh SJ, Greenhaff PL, Bankart J, Morgan MD, et al.

Dichloroacetate enhances performance and reduces blood lactate during maximal cycle

exercise in chronic obstructive pulmonary disease. American journal of respiratory and

critical care medicine. 2008 February; 177: p. 1090-1094.

61. P.K.J.Engelen M, Kasaburi R, Rucker R, Carithers E. Contribution of the Respiratory

Muscles to the Lactic Acidosis of heavy Exercises in COPD. CHEST. 1995 May; 108: p.

1246-1251.

62. Myers J, Ashley E. Dangerous Curve:A perspective on exercise,lactate,and the anaerobic

threshold. Chest. 1997 March; 111(3): p. 787-795.

63. Jacob DI. Blood lactate. Sports Medicine. 1986 jANUARY; 3(1): p. 10-25.

64. Moorcroft AJ, M.E.Dodd , J.Morris , A.K.Webb. Symptoms,lactate and exercise

limitation at peak cycle ergometry in adults with cystic fibrosis. Eur Respiratory Journal.

2005; 25(6): p. 1050-1056.

65. Westerblad H, Allen DG, Lännergren J. Muscle Fatigue: Lactic Acid or Inorganic

Phosphate the major cause? News Physiol. Sci. 2002 February; 17: p. 17-21.

66. O’Donnell DE. Hyperinflation, Dyspnea, and Exercise Intolerance in COPD. Am Thorac

Soc. 2006; 3: p. 180-184.

67. Katz A, Sahlin K. Role of oxygen in regulation of glycolysis and lactate production in

human skeletal muscle. Exercise and sports sciences review. 1990 January; 18(1): p. 1-

28.

68. Santos1 DB, Viegas CAdA. Correlation of levels of obstruction in COPD with lactate.

Revista Portuguea de Pneumologia. 2009 Januray; 15(1): p. 11-25.

69. TANAKA Y, HINO M, MORIKAWA T, TAKEUCHI K, MIZUNO K, KUDOH S.

Arterial blood lactate is a useful guide to when rehabilitation should be instigated in

COPD. Respirology. 2008 June; 13(4): p. 564-568.

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