Respiratory system is vital organ system of body,
illnesses of which may affect function of body as a whole. Respiratory
tract illnesses are of variable etiology and may be acute, sub-acute or
chronic. Development of Pediatric Pulmonology as a specialty in India is
steadily improving over past few decades. Formation of separate chapter
with name of "Respiratory Chapter" of Indian Academy of Pediatrics has
improved interaction among pediatricians who are practicing Pediatric
pulmonology or are interested in childhood respiratory illnesses. With
regular meetings, more young persons are getting attracted to this
specialty.
Burden of Respiratory Illnesses
In a recent estimate, about 1.682 million children
younger than 5 years died in 2010 in India. Of these, 0.397 million
(24%) died due to pneumonia alone [1]. It has been reported that
outpatient attendance attributed to acute respiratory infections is as
high as 20-40% of all outpatients and 12-35% of in-patients [2]. Burden
of asthma in school going children varies from 4%-20% in different parts
of India [3]. Apart from these illnesses, drug sensitive and drug
resistant pulmonary tuberculosis and Human immunodeficiency virus (HIV)
associated pulmonary illnesses also add to the burden of respiratory
illnesses. Other emerging diseases like cystic fibrosis,
bronchopulmonary dysplasia, interstitial lung diseases and opportunistic
infections in group of immunocompromised hosts, though do not form a
significant burden now, but are emerging as future challenges.
Acute respiratory tract infections
Acute respiratory tract infections (ARI) are one of
the leading causes of morbidity and acute lower respiratory tract
infection is the leading cause of mortality in children [1]. Government
of India launched ARI control program in the 1980s and it showed
improved survival in infants and under-five children. However, its
impact is less than desired. This is a major challenge for
pulmonologists and public health experts to reduce pneumonia-related
mortality in under-five age group. There is need to identify risk
factors for pneumonia related mortality and prevent deaths by
appropriate efforts. Emergence of drug resistance to commonly used drugs
like cotrimoxazole in common respiratory pathogens is one of the
important challenges [4,5]. Reasons for emergence of drug resistance
include indiscriminate use of antibiotics in respiratory tract
infection. Majority of upper respiratory tract infections (URTI) are due
to viral infections and do not need antibiotics. To reduce unnecessary
use of antibiotics in URTI, there is need to sensitize pediatricians for
its harmful effect. In this direction, IAP Respiratory Chapter developed
Respiratory Tract Infection Group Education Module (RTIGEMS) that aims
to educate pediatrician about rationale use of antibiotics [6].
World Health Organization recommended the
identification of community acquired pneumonia by clinical features
(cough with difficulty in breathing) and administration of antibiotics
to these patients. In ARI control program, children with wheeze may also
get treated with antibiotics unnecessarily. To overcome this problem,
modification in algorithm has been found to be useful [7] and same has
been suggested by an expert group [8].
Identification of causative microbial agents for
various respiratory tract infections is difficult and not cost effective
at present. Earlier bacterial pathogens were being recognized by an
invasive procedure like lung puncture [9]. Viral agents can be
identified by obtaining nasopharyngeal aspirates [10] and bacterial
pathogens by demonstration of antigen in urine [11] or by blood culture
[10]. With use of molecular diagnostic tests, it may be feasible to
identify causative agents for respiratory tract infection [12]. With
improvement in molecular diagnostics, it may be possible to make
informed decision for starting antibiotics in respiratory infection in
future.
Asthma: Changing Incidence, Treatment Protocols,
Future Prospects
Asthma is one of the commonest chronic illnesses for
visit to doctor and has significant social and economic impact [13].
First documented studies on asthma prevalence in India include a survey
conducted by Indian Council of Medical Research (ICMR) on central
government employees and their family members in 1961, and recorded
prevalence as 1.8% [14]. A study in Patna documented prevalence of 2.7%
in rural area and 1.6% in urban area [15]. More recent reports on asthma
prevalence (any wheeze in past 12 months) in school going children in
Indian subcontinent in ISAAC 1 and ISAAC 3 studies have reported
prevalence of 6.38% and 6.40% [16], suggesting that it has stabilized
now. However, going by the numbers, it will continue to remain a public
health problem. The treatment followed by pediatricians is still
suboptimal. Only one third of asthmatic patients receive standard
inhaled therapy [17]. Respiratory Chapter of the Indian Academy of
Pediatrics has prepared an evidence based treatment protocol to promote
standardized uniform treatment [18]. This is one step forward to improve
care of children with asthma.
With the recognition of various phenotypes of asthma,
it is important to identify and treat individuals accordingly. Diagnosis
of asthma still remains clinical in most instances. Newer drugs like
omalizumab are available in India. Though cost is limiting factor, but
is important therapeutic approach that may have potential role in
difficult to treat asthma.
Advances in immunotherapy for allergic diseases
including asthma has not been assessed to be useful in asthmatic
children possibly due to multiple phenotypes of asthma and good response
to inhaled steroids along with other medications. It also may have some
potential for treatment in selected difficult atopic asthmatic children
[19]. Some of the drugs like ciclosenide, long acting beta agonists,
leukotriene receptor antagonists (LTRA) etc have not been cleared for
use in all age groups. With more safety data they will also become part
of therapeutic armamentarium of asthma in India.
Pulmonary Manifestations of HIV Infection
HIV infection in children is a new illness over past
three decades. Respiratory illnesses are important cause of morbidity in
these children. These patients are at risk of recurrent respiratory
infections due to usual and unusual organisms. Apart from the usual
organisms (S. pneumoniae, H. influenzae, S. aureus)
these children are more prone for infections due to gram negative
bacilli, Pneumocystis jirovecii (PCP) and fungal infections. In
India, tuberculosis is the commonest opportunistic infection in HIV
infected children [20]. Non infectious illnesses like
lymphoproliferative disorders including lymphoid interstitial pneumonia
(LIP) is considered to be AIDS defining illness. Use of anti-retroviral
drugs and daily cotrimoxazole in children has reduced respiratory
infections due to usual organisms and PCP.
Molecular diagnostic test on induced sputum for
identification of PCP is one of the important advances and can be used
for management of immuno-compromised hosts, including children with HIV
infection [21].
Chronic Respiratory Diseases
In industrialized countries, the bulk of respiratory
illnesses in Pediatric Pulmonology services include: cystic fibrosis,
interstitial lung disease, gastroesophageal reflux diseases,
neuromuscular illnesses, sleep disorders, disorders due to
malformations, etc. Present profile of Indian pediatric chest services
include: asthma, recurrent infections, bronchiectasis, etc. It is
expected, that in future, this profile will change and will become
similar to that of industrialized countries.
Cystic fibrosis (CF) is leading, inherited,
life-limiting illness in Caucasian population. CF was considered to be
nonexistent in India. Recent review suggests that CF is probably
under-reported in India [22]. First documented Indian case of CF was
reported in 1968 [23]. Due to strong belief that CF is disease of
Caucasian population, diagnostic test, (sweat test/mutations/nasal
trans-membrane potential difference) were not developed and majority of
trained pediatrician, may not have seen single case of confirmed CF. Now
many centers have developed diagnostic facilities for CF and care of CF
patients. This is being reflected in form of sudden increase in number
of children with CF from different part of India.
Respiratory management of children with CF requires
systemic antibiotics. Another intervention in form of inhaled
antibiotics tobramycin/colistin is also available in the Indian market.
Mucolytic agent DNAse is not available in open market in India.
Hypertonic saline has been found to be an inexpensive substitute to
DNAse [24]. 3% hypertonic saline that is available in market has been
found to be equally effective [25]. Gastrointestinal management of CF
requires enteric coated spherules of pancreatic enzyme for use in
infants and children who cannot swallow enteric coated tablets, and is
available since 2004. Though at present there are few centers that
provide diagnostic and clinical care services, it is expected that in
future there will be need to develop more centers that can provide
services for CF patients. With increasing survival, more patients with
CF will survive into adulthood and there is need to develop liaison with
adult pulmonologists.
Primary ciliary dyskinesia is being recognized as
relatively common illness in pediatric respirology. Earlier the
diagnosis was based on classical clinical features and electron
microscopy and now genetic defect has been identified. Multiple
mutations have been reported in literature. A non-invasive test in form
of reduced fraction of exhaled nitric oxide (FENO) in these patients has
been used as screening test in some facilities. At present, these
patient require supportive care, but in future we expect development of
therapeutic intervention.
Interstitial lung diseases (ILD), though rare, are an
important cause of morbidity. ILDs are important illnesses in Pediatric
pulmonology services in industrialized countries. Till now, in India,
ILDs are limited to few case series [26-28]. Gold standard for the
diagnosis of ILD is lung biopsy. With improvement in
imaging/bronchoscopy, now all children with ILD may not need lung
biopsy. This will increase the number of patient that will get label of
ILD. The treatments of ILD depend on underlying cause. Many children
with ILD may need home oxygen therapy/home ventilation and other
supportive care. Home oxygen and ventilation are very poorly developed
in India. With increasing number of patient there is need to develop
expertise in this direction.
Gastroesophageal disease (GERD) and other syndromes
that cause passive aspirations are being recognized more frequently now.
Earlier diagnosis was based on endoscopic examination and biopsy of
esophagus. Now with availability of pH probe, it has become less
invasive and number of children with GERD has increased significantly.
Medical management is evolving and some patients may need surgical
intervention.
Other aspiration syndromes may be due to
malformations, neuromuscular problems or mental subnormality. These
patients are under diagnosed due to lack of awareness and burden of
other conditions. Management of such patients is challenging and needs a
team effort. Many such patients may need gastrostomies or feeding
jejunostomies for improving their nutrition and decreasing pulmonary
manifestations, and this requires collaborations with pediatric surgeons
and pediatric gastroenterologists.
Children born with major malformations like pulmonary
hypoplasia/agenesis, congenital diaphrag-matic hernia, congenital lobar
emphysema, cystic adenomatoid malformation, tracheoesophageal fistula,
bronchogenic and duplication cysts etc are now surviving with better
supportive care. They have significant morbidity in first few years of
life and require management expertise. At present, they are being
treated by pediatric surgeons or gastroenterologists. However, these
patients are better managed by pediatric pulmonologists and we need to
develop awareness and expertise in management of such patients. Children
with pulmonary vascular problems, with or without heart disease, are
also being recognized and need expertise for management [29,30].
In children, a common cause of obstructive sleep
apnea is upper airway obstruction due to adenoidal hypertrophy or
maxillofacial dysplasia. These can be corrected by surgical
intervention. More and more cases of central apnea are being reported
now. With identification of genetic markers for this syndrome, a
definitive diagnosis can be made. Screening tests and confirmation for
diagnosis by polysomnography are being developed in India.
Future Challenges
Pulmonary function tests: Children older than 5-7
years of age may undergo spirometry for diagnostic and monitoring
purpose. Demonstration of reversible airway obstruction is difficult in
preschool children. Now with advances in pulmonary function testing it
may be possible to document reversible airway obstruction in infants
using tidal breath flow volume loop (TBFVL), rapid thoracic compression
(RTC) or raised volume rapid thoracic compression (RVRTC) or whole body
plethysmography. For children above 3-4 years of age interrupter
technique and impulse oscillometry can also be used. These techniques
may not be available for routine use but some of them may have potential
for clinical utility in future. Some experience with spirometry
documenting normal values of parameters have been reported from
different part of India [31-35].
Bronchoscopy and bronchoalveolar lavage: Flexible
fibre optic bronchoscopy (FOB) is one of the important techniques in
pulmonary services. It is available in few centers and going by the
indications, we may need to develop bronchoscopy services in more
centers. Some experience of bronchoscopy and its utility has been
reported from various part of India [36-39]. At present transbronchial
ultrasound and biopsy is possible only with large size bronchoscope (6
mm external diameter), that may not be useful for young children.
However, with better technology, it may be available for smaller
bronchoscope also. Some centers are using FOB for removal of foreign
bodies [40]. In near future, other interventions in form of balloon
dilatation, whole lung lavage, etc may be available at some centers.
Sweat testing and mutation analysis for diagnosis of
cystic fibrosis: The facility for sweat test has been developed in
multiple centers over past one decade. However, going by size of India
there is need to develop more centers. Commercially available sweat test
equipment use pilocarpine iontophoresis for sweat collection and
estimation is done by measuring conductivity or osmolality (Vescor
Macroduct sweat collecting system). Some centers are using indigenous
method of sweat chloride estimation [41]. More than 1600 mutations have
already been identified and the mutations are heterogenous in Indian
children with CF [42], and there is no common panel of mutations that
can detect all children with CF, sweat chloride still remains gold
standard for making a diagnosis of CF. In future with more experience,
possibly we may have region specific mutation panel for easy diagnosis
of CF.
Radiology and nuclear imaging: These facilities
are available in public and private services and pediatricians are using
them for diagnosis and management of various respiratory conditions.
There is need to create interest among radiologists in each center who
are more interested in pediatric pulmonary images to improve diagnostic
yield of imaging in children.
Sleep studies: Sleep problems are emerging
morbidity in children. Some centers are performing sleep studies in
children. There is need to develop indications for sleep studies in
India [43].
At present there is no formal degree course in
Pediatric pulmonology. However, going by the burden of illness and scope
of subject there is huge scope in pediatric pulmonology specialty.
Initially, middle level pediatricians who want to pursue their career in
pediatric pulmonology should undergo long term or short term training in
existing centers. Trained persons should develop network to collect data
and answer relevant research questions.
1. Liu L, Johnson HL, Cousens S, Perin J, Scott S,
Lawn JE, et al. Child Health Epidemiology Reference Group of WHO
and UNICEF. Global, regional, and national causes of child mortality: an
updated systematic analysis for 2010 with time trends since 2000.
Lancet. 2012;379:2151-61.
2. Jain N, Lodha R, Kabra SK. Upper respiratory tract
infections. Indian J Pediatr. 2001;68:1135-8.
3. The International Study of Asthma and Allergies in
Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence
of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema:
ISAAC. Lancet. 1998; 351:1225-32.
4. Goyal R, Singh NP, Kaur M, Talwar V. Antimicrobial
resistance in invasive and colonising Streptococcus pneumoniae in
North India. Indian J Med Microbiol. 2007;25:256-9.
5. Das BK, Arora NK, Mathur P, Ostwal P, Mandal S,
Kabra SK, et al. Nasopharyngeal carriage of Haemophilus
influenzae. Indian J Pediatr. 2002;69: 775-7.
6. RTI facts: Bugs, Drugs and You. IAP Consensus
Guideline on rational Management of Respiratory Tract Infections in
Children. Indian Academy of Pediatrics, 2006.
7. Sachdev HP, Vasanthi B, Satyanarayana L, Puri RK.
Simple predictors to differentiate acute asthma from ARI in children:
implications for refining case management in the ARI Control Programme.
Indian Pediatr. 1994;31:1251-9.
8. India Clinical Epidemiology Network (IndiaCLEN)
Task Force on Pneumonia. Rational use of antibiotics for pneumonia.
Indian Pediatr. 2010;47:11-8.
9. Sinha DP, Hughes JR. Lung tap in lower respiratory
tract infections in children. Indian Pediatr. 1966;3:385-92.
10. Kabra SK, Lodha R, Broor S, Chaudhary R, Ghosh M,
Maitreyi RS. Etiology of acute lower respiratory tract infection. Indian
J Pediatr. 2003;70:33-6.
11. Mermond S, Zurawski V, D’Ortenzio E, Driscoll AJ,
DeLuca AN, Deloria-Knoll M, et al. Lower respiratory infections
among hospitalized children in New Caledonia: a pilot study for the
Pneumonia Etiology Research for Child Health project. Clin Infect Dis.
2012;54:S180-9.
12. Bharaj P, Sullender WM, Kabra SK, Mani K, Cherian
J, Tyagi V, et al. Respiratory viral infections detected by
multiplex PCR among pediatric patients with lower respiratory tract
infections seen at an urban hospital in Delhi from 2005 to 2007. Virol
J. 2009;6:89.
13. Lodha R, Puranik M, Kattal N, Kabra SK. Social
and economic impact of childhood asthma. Indian Pediatr.. 2003;40:874-9.
14. Viswanathan R, Mody RK, Prasad SS, Sinha SP.
Bronchial asthma and chronic bronchitis. A pilot survey. J Indian Med
Assoc. 1965;45:480-3.
15. Viswanathan R, Prasad M, Thakur AK, Sinha SP,
Prakash N, Mody RK, et al. Epidemiology of asthma in an urban
population. A random morbidity survey. J Indian Med Assoc.
1966;46:480-3.
16. Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil
U, Mitchell E, et al. Worldwide trends in the prevalence of
asthma symptoms: phase III of the International Study of Asthma and
Allergies in Childhood (ISAAC). Thorax. 2007;62:758-66.
17. Srivastava R, Sharma S, Keshri L, Wal P.
Assessment of prescription pattern in asthma therapy at Shamli
hospitals. Rev Recent Clin Trials. 2012;7:158-64;
18. Asthma By Consensus (ABC): Consensus Statement on
the Diagnosis and Management of Asthma in Children. Indian Academy of
Pediatrics, 2003.
http://www.iapindia.org/iap-resources/web-links/recommendations-a-guidelines.
19. Frew AJ. Allergen immunotherapy. J Allergy Clin
Immunol. 2010;125:S306-13. .
20. Merchant RH, Lala MM. Common clinical problems in
children living with HIV/AIDS: systemic approach. Indian J Pediatr. 2012
Sep 27. [Epub ahead of print].
21. Gupta R, Mirdha BR, Guleria R, Kumar L,
Samantaray JC, Agarwal SK, Kabra SK, et al. Diagnostic
significance of nested polymerase chain reaction for sensitive detection
of Pneumocystis jirovecii in respiratory clinical specimens.
Diagn Microbiol Infect Dis. 2009;64:381-8.
22. Kabra SK, Kabra M, Lodha R, Shastri S. Cystic
fibrosis in India. Pediatr Pulmonol. 2007;42:1087-94.
23. Bhakoo ON, Kumar R, Walia BN. Mucoviscidosis of
the lung. Report of a case.Indian J Pediatr. 1968;35:183-5.
24. Donaldson SH, Bennett WD, Zeman KL, Knowles MR,
Tarran R, Boucher RC. Mucus clearance and lung function in cystic
fibrosis with hypertonic saline. N Engl J Med. 2006;354:241-50.
25. Gupta S, Ahmed F, Lodha R, Gupta YK, Kabra SK.
Comparison of effects of 3 and 7% hypertonic saline nebulization on lung
function in children with cystic fibrosis: A double-blind randomized,
controlled trial. J Trop Pediatr. 2012 [Epub ahead of print] .
26. Sankar J, Pillai MS, Sankar MJ, Lodha R, Kabra
SK. Clinical profile of interstitial lung disease in children. Indian
Pediatr. 2012 Jun 10. [Epub ahead of print].
27. Vijayasekaran D, Giridhar S, Gowrishankar NC,
Nedunchelian K, Senguttuvan M. Pediatric interstitial lung disease.
Indian Pediatr. 2006;43:899-903.
28. Balasubramanian S, Janakiraman L, Ganesh R,
Deenadayalan M, Naidu RK. Interstitial lung disease in infancy. Indian J
Pediatr. 2007;74:637-9.
29. Vaideeswar P, Tullu MS, Lahiri KR, Pandit SP.
Pulmonary endarteritis. Indian J Pediatr. 2006;73:1130-2.
30. Krishnan U. Diagnosis and management of primary
pulmonary hypertension. Indian J Pediatr. 2000l;67:523-7.
31. Raju PS, Prasad KV, Ramana YV, Murthy KJ.
Pulmonary function tests in Indian girls- prediction equations. Indian J
Pediatr. 2004;71:893-7.
32. Sharma PP, Gupta P, Deshpande R, Gupta P. Lung
function values in healthy children (10-15 years). Indian J Pediatr.
1997;64:85-91.
33. Swaminathan S, Diffey B, Vaz M. Evaluating the
suitability of prediction equations for lung function in Indian
children: a practical approach. Indian Pediatr. 2006;43:680-98.
34. Srivastava A, Kapoor RK, Misra PK, Srivastava KL,
Thakur S, Shukla N. Pulmonary function tests in normal Indian children
and changes in respiratory disorders. Indian Pediatr. 1995;32:629-34.
35. Sethi GR, Gupta A, Bhatnagar OP, Jain AK. Dynamic
lung volumes in children with bronchial asthma. Indian Pediatr.
1987;24:543-7.
36. Kabra SK, Lodha R, Ramesh P, Sarthi M. Fiberoptic
bronchoscopy in children an audit from a tertiary care center. Indian
Pediatr. 2008;45:917-9.
37. Singh M, Rao KL, Kumar L. Role of flexible
fiberoptic bronchoscopy in the diagnosis of tracheobronchial foreign
bodies in children. Indian Pediatr. 1999;36: 386-9.
38. Somu N, Vijayasekaran D, Ashok TP, Balachandran
A, Subramanyam L. Flexible fibreoptic bronchoscopy in 582 children—value
of route, sedation and local anesthetic. Indian Pediatr. 1995;32:543-7.
39. Vijayasekaran D, Kalpana S, Ramachandran P,
Nedunchelian K. Indications and outcome of flexible bronchoscopy in
neonates. Indian J Pediatr. 2012;79:1181-4.
40. Singh V, Tak MU, Kimini I, Parakh A. Flexible
bronchoscopic extraction of tracheobronchial foreign bodies in children:
lessons learnt – a 10 year experience from North India. Pediatr Resp
Review. 2012:13:S 73.
41. Kabra SK, Kabra M, Gera S, Lodha R, Sreedevi KN,
Chacko S, et al. An indigenously developed method for sweat
collection and estimation of chloride for diagnosis of cystic fibrosis.
Indian Pediatr. 2002;39:1039-43.
42. Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon
PS. Characterization of mutations and genotype-phenotype correlation in
cystic fibrosis: experience from India. J Cyst Fibros. 2008;7:110-5.
43. Sukumaran TU. Pediatric sleep project. Indian Pediatr.
2011;48:843-4.