Nicod, L.P.

Frontiers in Medicine

PubMed

Laurent Pierre Nicod

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A grand challenge of factors influencing lung health

Serveur académique lausannois

MEDICINESPECIALTY GRAND CHALLENGE ARTICLEpublished: 01 May 2014doi: 10.3389/fmed.2014.00011A grand challenge of factors influencing lung healthLaurent P. Nicod*Service of Pneumology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland*Correspondence: laurent.nicod@chuv.chEdited and reviewed by:Bethany B. Moore, University of Michigan, USAKeywords: lung health, lung diseases, lifestyle factors, environmental factors, biomarkersRespiratory diseases whether communica-ble or non-communicable, acute or chronicimpact on health of millions of people.Several research areas, strongly linkedto the pathogenesis of respiratory diseaseshave been identified as priorities over-arching different specialties (1, 2). Someare related to early origin of lung dis-ease. Lifestyle choices have obvious conse-quences as well as environmental factorsrelated to inhaled particles or pathogensimpacting the integrity of the airways, orof our microbiote with dysbiose. Lungdefenses are important to preserve ourlungs from aggression. Their changes in lifeare important allowing more vulnerabilityearly in childhood as well as late in life.Lung diseases are more frequent with agingand this represents several challenges.The early origin of lung diseases shouldbe better analyzed to understand lungdevelopment and prevent diseases impact-ing adulthood (3). Prenatal factors areknown to influence lung health later inlife with both nutritional deficiencies andmaternal smoking already recognized ashaving epigenetic and trans-generationaleffects (4). Life expectancy of several con-genital defects has improved as infants withcystic fibrosis or neuromuscular diseasebenefit from early interventions with newtargeted biological approaches (5). Effec-tive prevention of several early infectionsis important, in order to reduce incidenceof premature death or bronchiolitis withlong term sequelae. The role of microbiotefor the education of the immune systemappear an important challenge, to preventallergies to common allergens in the formof rhinitis or asthma of varying severity,often persisting into adulthood (6, 7).Lifestyle can impact lung healthmarkedly. It is established that nutritionaldeficiencies impair lung growth, favorinfections, and can decrease the ability tocontrol inflammatory processes due, forinstance, to lack of antioxidative factors (8,9). A decrease of physical activity, oftencombined with obesity, impacts on disor-ders such as asthma. Obesity also leads toobstructive sleep apnea syndrome (OSAS)(10). The overall cardiovascular and meta-bolic consequences of OSAS are now rec-ognized to be significant and add to theoverall burden of diseases. The physiologicprocess involved need to be better under-stood. Inhaled particles, volatile organiccompounds, active and passive smoking aremajor factors in the etiology of chronicobstructive lung diseases (COPD) (11).Asthma and COPD are the most prevalentrespiratory diseases placing a major burdenon health care systems. The local and sys-temic effects of these diseases still deserveintensive research for prevention and newtargeted therapies.Among the environmental factors, car-cinogens found in tobacco smoke areknown to be abundant and contribute toone of the two most frequent cancers,which is lung cancer, the first in menand the second in women. Other carcino-gens include the radioactive element radon,which may be released naturally from thegranite below houses (12), or asbestosextracted from mines and used for buildinginsulation. All such compounds need to beidentified and environmental exposure tothem minimized.Lung defenses and infections are atthe crossroads of several specialties. Theintegration of our knowledge is impor-tant, as acute lower respiratory infections(such as bacterial and viral pneumonia,influenza, and respiratory syncytial virusinfections) are the third most frequentcause of death worldwide, accounting for4.25 million deaths each year. Underly-ing chronic lung diseases often alter lungdefenses and influence the type infectionfound (13, 14). Several chronic lung dis-eases like interstitial lung disease, cysticfibrosis, or asthma among other chronicobstructive disease can be markedly exac-erbated by the occurrence of infections(15). Preventions of infections and con-trol of inflammation induced in such cir-cumstances are challenges for the future.New vaccines and antiviral agents are alsoneeded.Aging causes a reduction in the gas-exchange surface of the lungs, which maylead to a reduced capacity to oxygenateblood. The airways become more collapsi-ble, worsening any underlying obstructivedisease (16). Lung defenses are altered andinfections increased in frequency (17). Pre-vention of undue inflammation related toenvironmental factors might decrease theeffects of this natural decline in airwayfunction. Lung injury related to inhaledparticles or to infections can producefibrotic processes related to defects in nat-ural repair, to alterations in lung matrixwith consequences in diseases like lungfibrosis and/or to a higher incidence ofautoimmune diseases among older peo-ple (18). The immune process lead notonly to scaring of distal airways, but alsoin some patients to vascular narrowingand to a higher incidence of pulmonaryarterial hypertension with age (19). Withaging, dysregulation of lung tissue regener-ation by progenitor cells can occur, leadingto various thoracic malignancies. Malig-nancy is also related to carcinogens or togenetic factors and identification of thesemay result in more individualized diag-nostic screening and more personalizedtreatment.New technologies are becoming avail-able for improved imaging, with more spe-cific biomarkers and for more precise tar-geting of metabolic pathways. These shouldallow earlier and more specific diagnosis,www.frontiersin.org May 2014 | Volume 1 | Article 11 | 1Nicod Challenges in modern pulmonary medicineas well as better targeted and personalizedtreatments. One can hope that these newdevelopments will decrease side effects ofcurrent therapies, improving disease out-comes and promote more healthy aging.Frontiers in pneumology should reflect allthese new developments.REFERENCES1. Nicod LP, Kamel N, Ward B, Decramer M, SibilleY, Lambrecht B, et al. ERS is founding memberof a new Alliance for Biomedical Research inEurope. Eur Respir J (2011) 38(2):237–8. doi:10.1183/09031936.000935112. Gibson GJ, Loddenkemper R, Lundback B, SibilleY.Respiratory health and disease in Europe: the newEuropean Lung White Book. Eur Respir J (2013)42(3):559–63. doi:10.1183/09031936.001055133. Baraldi E, Filippone M. Chronic lung diseaseafter premature birth. N Engl J Med (2007)357(19):1946–55. doi:10.1056/NEJMra0672794. Kabesch M, Michel S, Tost J. Epigenetic mecha-nisms and the relationship to childhood asthma.Eur Respir J (2010) 36(4):950–61. doi:10.1183/09031936.000193105. Grasemann H, Ratjen F. Emerging therapies forcystic fibrosis lung disease. Expert Opin EmergDrugs (2010) 15(4):653–9. doi:10.1517/14728214.2010.5177466. Marsland BJ. Influences of the microbiome onthe early origins of allergic asthma. Ann AmThorac Soc (2013) 10(Suppl):S165–9. doi:10.1513/AnnalsATS.201305-118AW7. Trompette A, Gollwitzer ES, Yadava K, SichelstielAK, Sprenger N, Ngom-Bru C, et al. Gut micro-biota metabolism of dietary fiber influences aller-gic airway disease and hematopoiesis. Nat Med(2014) 20(2):159–66. doi:10.1038/nm.34448. Samolinski B, Fronczak A, Wlodarczyk A, Bous-quet J. Council of the European Union con-clusions on chronic respiratory diseases in chil-dren. Lancet (2012) 379(9822):e45–6. doi:10.1016/S0140-6736(12)60513-39. Bentley AR, Kritchevsky SB, Harris TB, HolvoetP, Jensen RL, Newman AB, et al. Dietary antioxi-dants and forced expiratory volume in 1 s decline:the Health, Aging and Body Composition Study.Eur Respir J (2012) 39(4):979–84. doi:10.1183/09031936.0019001010. ten Hacken NH. Physical inactivity and obe-sity: relation to asthma and chronic obstructivepulmonary disease? Proc Am Thorac Soc (2009)6(8):663–7. doi:10.1513/pats.200907-070DP11. Sigsgaard T, Nowak D, Annesi-Maesano I, NemeryB, Toren K, Viegi G, et al. ERS position paper:work-related respiratory diseases in the EU.Eur Respir J (2010) 35(2):234–8. doi:10.1183/09031936.0013940912. Turner MC, Krewski D, Chen Y, Pope CA III,Gapstur SM, Thun MJ. Radon and COPD mor-tality in the American Cancer Society Cohort.Eur Respir J (2012) 39(5):1113–9. doi:10.1183/09031936.0005821113. Whitters D, Stockley R. Immunity and bac-terial colonisation in bronchiectasis. Thorax(2012) 67(11):1006–13. doi:10.1136/thoraxjnl-2011-20020614. Viasus D, Pano-Pardo JR, Cordero E, CampinsA, Lopez-Medrano F, Villoslada A, et al. Effectof immunomodulatory therapies in patients withpandemic influenza A (H1N1) 2009 complicatedby pneumonia. J Infect (2011) 62(3):193–9. doi:10.1016/j.jinf.2011.01.01415. Asner S, Waters V, Solomon M, Yau Y, RichardsonSE, Grasemann H, et al. Role of respiratory virusesin pulmonary exacerbations in children with cysticfibrosis. J Cyst Fibros (2012) 11(5):433–9. doi:10.1016/j.jcf.2012.04.00616. Ito K, Barnes PJ. COPD as a disease of accel-erated lung aging. Chest (2009) 135(1):173–80.doi:10.1378/chest.08-141917. Meyer KC. The role of immunity and inflam-mation in lung senescence and susceptibility toinfection in the elderly. Semin Respir Crit CareMed (2010) 31(5):561–74. doi:10.1055/s-0030-126589718. Castriotta RJ, Eldadah BA, Foster WM, HalterJB, Hazzard WR, Kiley JP, et al. Workshop onidiopathic pulmonary fibrosis in older adults.Chest (2010) 138(3):693–703. doi:10.1378/chest.09-300619. Lam CS, Borlaug BA, Kane GC, Enders FT, Rode-heffer RJ, Redfield MM. Age-associated increases inpulmonary artery systolic pressure in the generalpopulation. Circulation (2009) 119(20):2663–70.doi:10.1161/CIRCULATIONAHA.108.838698Conflict of Interest Statement: The author declaresthat the research was conducted in the absence of anycommercial or financial relationships that could beconstrued as a potential conflict of interest.Received: 27 March 2014; accepted: 16 April 2014;published online: 01 May 2014.Citation: Nicod LP (2014) A grand challenge of fac-tors influencing lung health. Front. Med. 1:11. doi:10.3389/fmed.2014.00011This article was submitted to Pulmonary Medicine, asection of the journal Frontiers in Medicine.Copyright © 2014 Nicod. This is an open-access articledistributed under the terms of the Creative CommonsAttribution License (CC BY). The use, distribution orreproduction in other forums is permitted, provided theoriginal author(s) or licensor are credited and that theoriginal publication in this journal is cited, in accordancewith accepted academic practice. No use, distribution orreproduction is permitted which does not comply withthese terms.Frontiers in Medicine | Pulmonary Medicine May 2014 | Volume 1 | Article 11 | 2

A grand challenge of factors influencing lung health.

Laurent P. Nicod

Frontiers - Publisher Connector

A Grand Challenge of Factors Influencing Lung Health

MEDICINE
SPECIALTY GRAND CHALLENGE ARTICLE
published: 01 May 2014
doi: 10.3389/fmed.2014.00011
A grand challenge of factors influencing lung health
Laurent P. Nicod*
Service of Pneumology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
*Correspondence: laurent.nicod@chuv.ch
Edited and reviewed by:
Bethany B. Moore, University of Michigan, USA
Keywords: lung health, lung diseases, lifestyle factors, environmental factors, biomarkers
Respiratory diseases whether communica-
ble or non-communicable, acute or chronic
impact on health of millions of people.
Several research areas, strongly linked
to the pathogenesis of respiratory diseases
have been identified as priorities over-
arching different specialties (1, 2). Some
are related to early origin of lung dis-
ease. Lifestyle choices have obvious conse-
quences as well as environmental factors
related to inhaled particles or pathogens
impacting the integrity of the airways, or
of our microbiote with dysbiose. Lung
defenses are important to preserve our
lungs from aggression. Their changes in life
are important allowing more vulnerability
early in childhood as well as late in life.
Lung diseases are more frequent with aging
and this represents several challenges.
The early origin of lung diseases should
be better analyzed to understand lung
development and prevent diseases impact-
ing adulthood (3). Prenatal factors are
known to influence lung health later in
life with both nutritional deficiencies and
maternal smoking already recognized as
having epigenetic and trans-generational
effects (4). Life expectancy of several con-
genital defects has improved as infants with
cystic fibrosis or neuromuscular disease
benefit from early interventions with new
targeted biological approaches (5). Effec-
tive prevention of several early infections
is important, in order to reduce incidence
of premature death or bronchiolitis with
long term sequelae. The role of microbiote
for the education of the immune system
appear an important challenge, to prevent
allergies to common allergens in the form
of rhinitis or asthma of varying severity,
often persisting into adulthood (6, 7).
Lifestyle can impact lung health
markedly. It is established that nutritional
deficiencies impair lung growth, favor
infections, and can decrease the ability to
control inflammatory processes due, for
instance, to lack of antioxidative factors (8,
9). A decrease of physical activity, often
combined with obesity, impacts on disor-
ders such as asthma. Obesity also leads to
obstructive sleep apnea syndrome (OSAS)
(10). The overall cardiovascular and meta-
bolic consequences of OSAS are now rec-
ognized to be significant and add to the
overall burden of diseases. The physiologic
process involved need to be better under-
stood. Inhaled particles, volatile organic
compounds, active and passive smoking are
major factors in the etiology of chronic
obstructive lung diseases (COPD) (11).
Asthma and COPD are the most prevalent
respiratory diseases placing a major burden
on health care systems. The local and sys-
temic effects of these diseases still deserve
intensive research for prevention and new
targeted therapies.
Among the environmental factors, car-
cinogens found in tobacco smoke are
known to be abundant and contribute to
one of the two most frequent cancers,
which is lung cancer, the first in men
and the second in women. Other carcino-
gens include the radioactive element radon,
which may be released naturally from the
granite below houses (12), or asbestos
extracted from mines and used for building
insulation. All such compounds need to be
identified and environmental exposure to
them minimized.
Lung defenses and infections are at
the crossroads of several specialties. The
integration of our knowledge is impor-
tant, as acute lower respiratory infections
(such as bacterial and viral pneumonia,
influenza, and respiratory syncytial virus
infections) are the third most frequent
cause of death worldwide, accounting for
4.25 million deaths each year. Underly-
ing chronic lung diseases often alter lung
defenses and influence the type infection
found (13, 14). Several chronic lung dis-
eases like interstitial lung disease, cystic
fibrosis, or asthma among other chronic
obstructive disease can be markedly exac-
erbated by the occurrence of infections
(15). Preventions of infections and con-
trol of inflammation induced in such cir-
cumstances are challenges for the future.
New vaccines and antiviral agents are also
needed.
Aging causes a reduction in the gas-
exchange surface of the lungs, which may
lead to a reduced capacity to oxygenate
blood. The airways become more collapsi-
ble, worsening any underlying obstructive
disease (16). Lung defenses are altered and
infections increased in frequency (17). Pre-
vention of undue inflammation related to
environmental factors might decrease the
effects of this natural decline in airway
function. Lung injury related to inhaled
particles or to infections can produce
fibrotic processes related to defects in nat-
ural repair, to alterations in lung matrix
with consequences in diseases like lung
fibrosis and/or to a higher incidence of
autoimmune diseases among older peo-
ple (18). The immune process lead not
only to scaring of distal airways, but also
in some patients to vascular narrowing
and to a higher incidence of pulmonary
arterial hypertension with age (19). With
aging, dysregulation of lung tissue regener-
ation by progenitor cells can occur, leading
to various thoracic malignancies. Malig-
nancy is also related to carcinogens or to
genetic factors and identification of these
may result in more individualized diag-
nostic screening and more personalized
treatment.
New technologies are becoming avail-
able for improved imaging, with more spe-
cific biomarkers and for more precise tar-
geting of metabolic pathways. These should
allow earlier and more specific diagnosis,
www.frontiersin.org May 2014 | Volume 1 | Article 11 | 1
Nicod Challenges in modern pulmonary medicine
as well as better targeted and personalized
treatments. One can hope that these new
developments will decrease side effects of
current therapies, improving disease out-
comes and promote more healthy aging.
Frontiers in pneumology should reflect all
these new developments.
REFERENCES
1. Nicod LP, Kamel N, Ward B, Decramer M, Sibille
Y, Lambrecht B, et al. ERS is founding member
of a new Alliance for Biomedical Research in
Europe. Eur Respir J (2011) 38(2):237–8. doi:10.
1183/09031936.00093511
2. Gibson GJ, Loddenkemper R, Lundback B, SibilleY.
Respiratory health and disease in Europe: the new
European Lung White Book. Eur Respir J (2013)
42(3):559–63. doi:10.1183/09031936.00105513
3. Baraldi E, Filippone M. Chronic lung disease
after premature birth. N Engl J Med (2007)
357(19):1946–55. doi:10.1056/NEJMra067279
4. Kabesch M, Michel S, Tost J. Epigenetic mecha-
nisms and the relationship to childhood asthma.
Eur Respir J (2010) 36(4):950–61. doi:10.1183/
09031936.00019310
5. Grasemann H, Ratjen F. Emerging therapies for
cystic fibrosis lung disease. Expert Opin Emerg
Drugs (2010) 15(4):653–9. doi:10.1517/14728214.
2010.517746
6. Marsland BJ. Influences of the microbiome on
the early origins of allergic asthma. Ann Am
Thorac Soc (2013) 10(Suppl):S165–9. doi:10.1513/
AnnalsATS.201305-118AW
7. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel
AK, Sprenger N, Ngom-Bru C, et al. Gut micro-
biota metabolism of dietary fiber influences aller-
gic airway disease and hematopoiesis. Nat Med
(2014) 20(2):159–66. doi:10.1038/nm.3444
8. Samolinski B, Fronczak A, Wlodarczyk A, Bous-
quet J. Council of the European Union con-
clusions on chronic respiratory diseases in chil-
dren. Lancet (2012) 379(9822):e45–6. doi:10.1016/
S0140-6736(12)60513-3
9. Bentley AR, Kritchevsky SB, Harris TB, Holvoet
P, Jensen RL, Newman AB, et al. Dietary antioxi-
dants and forced expiratory volume in 1 s decline:
the Health, Aging and Body Composition Study.
Eur Respir J (2012) 39(4):979–84. doi:10.1183/
09031936.00190010
10. ten Hacken NH. Physical inactivity and obe-
sity: relation to asthma and chronic obstructive
pulmonary disease? Proc Am Thorac Soc (2009)
6(8):663–7. doi:10.1513/pats.200907-070DP
11. Sigsgaard T, Nowak D, Annesi-Maesano I, Nemery
B, Toren K, Viegi G, et al. ERS position paper:
work-related respiratory diseases in the EU.
Eur Respir J (2010) 35(2):234–8. doi:10.1183/
09031936.00139409
12. Turner MC, Krewski D, Chen Y, Pope CA III,
Gapstur SM, Thun MJ. Radon and COPD mor-
tality in the American Cancer Society Cohort.
Eur Respir J (2012) 39(5):1113–9. doi:10.1183/
09031936.00058211
13. Whitters D, Stockley R. Immunity and bac-
terial colonisation in bronchiectasis. Thorax
(2012) 67(11):1006–13. doi:10.1136/thoraxjnl-
2011-200206
14. Viasus D, Pano-Pardo JR, Cordero E, Campins
A, Lopez-Medrano F, Villoslada A, et al. Effect
of immunomodulatory therapies in patients with
pandemic influenza A (H1N1) 2009 complicated
by pneumonia. J Infect (2011) 62(3):193–9. doi:
10.1016/j.jinf.2011.01.014
15. Asner S, Waters V, Solomon M, Yau Y, Richardson
SE, Grasemann H, et al. Role of respiratory viruses
in pulmonary exacerbations in children with cystic
fibrosis. J Cyst Fibros (2012) 11(5):433–9. doi:10.
1016/j.jcf.2012.04.006
16. Ito K, Barnes PJ. COPD as a disease of accel-
erated lung aging. Chest (2009) 135(1):173–80.
doi:10.1378/chest.08-1419
17. Meyer KC. The role of immunity and inflam-
mation in lung senescence and susceptibility to
infection in the elderly. Semin Respir Crit Care
Med (2010) 31(5):561–74. doi:10.1055/s-0030-
1265897
18. Castriotta RJ, Eldadah BA, Foster WM, Halter
JB, Hazzard WR, Kiley JP, et al. Workshop on
idiopathic pulmonary fibrosis in older adults.
Chest (2010) 138(3):693–703. doi:10.1378/chest.
09-3006
19. Lam CS, Borlaug BA, Kane GC, Enders FT, Rode-
heffer RJ, Redfield MM. Age-associated increases in
pulmonary artery systolic pressure in the general
population. Circulation (2009) 119(20):2663–70.
doi:10.1161/CIRCULATIONAHA.108.838698
Conflict of Interest Statement: The author declares
that the research was conducted in the absence of any
commercial or financial relationships that could be
construed as a potential conflict of interest.
Received: 27 March 2014; accepted: 16 April 2014;
published online: 01 May 2014.
Citation: Nicod LP (2014) A grand challenge of fac-
tors influencing lung health. Front. Med. 1:11. doi:
10.3389/fmed.2014.00011
This article was submitted to Pulmonary Medicine, a
section of the journal Frontiers in Medicine.
Copyright © 2014 Nicod. This is an open-access article
distributed under the terms of the Creative Commons
Attribution License (CC BY). The use, distribution or
reproduction in other forums is permitted, provided the
original author(s) or licensor are credited and that the
original publication in this journal is cited, in accordance
with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with
these terms.
Frontiers in Medicine | Pulmonary Medicine May 2014 | Volume 1 | Article 11 | 2


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