Interstitial lung disease (ILD) is a generic
term used to denote a heterogenous group of disorders involving the
pulmonary interstitium, presenting with common clinical features(1). In
addition to the interstitium, alveolar and distal air spaces are also
invariably involved in ILD. Though ILD occurs usually in adults,
pediatric populations do succumb to this condition.
Most children with ILD share a common presentation,
with signs and symptoms of restrictive lung disease. Both noninvasive
and invasive tests aid in the diagnosis of ILD but lung biopsy remains
the gold standard(2). Since the differential diagnosis of ILD includes
more than 100 conditions in adults and children(1,3), it presents
enormous diagnostic challenges. Therefore, studies on the predisposing
environmental factors, diagnostic approach and response to treatment
regimens of pediatric ILD are the need of the hour. We conducted a
retrospective analysis to study the symptomatology, clinical features
and investigations of ILD in children.
Subjects and Methods
Children admitted in the Pediatric Pulmonology
Department of the Institute of Child Health and Hospital for Children,
Chennai, during the 4-year period between June 2000 and May 2004 with
progressive cough, dyspnea, and chest X-ray/High Resolution
Computerized Tomography (HRCT) abnormalities suggestive of ILD were
included in the study. Chest X-ray findings of bilateral
reticular shadows at the base of the lungs and/or peripheral
interstitial changes as suggested by diffuse infiltrates and ground
glass appearance; and HRCT findings of ground glass attenuation and
interstitial thickening, with/without nodules, honey-combing,
parenchymal distortion and traction bronchiectasis, were the findings
interpreted as consistent with ILD(4). The data was retrieved from the
Medical Records Depart-ment of the hospital. Children who were diagnosed
as bronchopulmonary dysplasia, congenital heart disease, primary
malignancy, primary immunodeficiency, and primary autoimmune disorders
were excluded from the analysis.
An analysis of presenting symptoms, past history and
clinical findings was done. In addition to the basic investigations, the
results of spirometry, serial chest skiagrams, HRCT, bronchoalveolar
lavage (BAL) and lung biopsy were evaluated.
Results
Sixteen cases were included in the analysis. Seven
cases (43.8%) had onset of symptoms in infancy (Table
I). The mean duration of symptoms
at presentation was 12.81 months (range 2 to 24 months), with 4 cases
(25%) having an acute presentation of <3 months(5). The mean time
interval between initial presentation to the institution and the
diagnosis of suspected/confirmed ILD was 3.93 months (range 1 month to
12 months).
Velcro crackles were the commonest physical finding,
present in 15 cases (93.8%). Ten cases (62.5%) were undernourished and
pulmonary hypertension confirmed by echocardiogram was present in 5
cases (31.5%). Skin lesions in the form of erythematous maculopapular
rashes were noticed in 4 cases (25%) and these persisted during follow
up examinations
Routine blood investigations were not contributory in
any of the cases. A workup for tuberculosis (Mantoux, resting gastric
juice analysis for acid fast bacilli and screening of parents for
tuberculosis) was negative in all cases.
The chest X-rays were initially abnormal in
all cases but commonly reported as broncho-pneumonia. Though initial
X-rays were not contributory in any case, serial X-rays
revealed findings suggestive of ILD in 12 cases (75%).
HRCT of the chest was done subsequently in all but
one case. The HRCT findings were consistent with ILD in 13 cases
(86.6%). Four cases, where chest X-rays did not aid in the
diagnosis, had HRCT findings suggesting ILD. HRCT revealed bilateral
findings and lower lung zone involvement in all cases. Ground glass
opacification was the commonest radiological abnormality, seen in all
the cases, followed by interstitial thickening in 7 cases (53.84%) and
interlobular septal thickening, traction bronchiectasis and honeycomb
pattern in 3 cases (23.07%).
Hypoxemia was documented by blood gas analysis in all
the patients. Spirometry, done in 5 children (31.2%), showed a
restrictive pattern from the time of initial presentation, with a
progressive reduction of forced vital capacity. BAL analysis done in 8
cases (50%) revealed the presence of increased inflammatory cells in
all cases, mainly neutrophils, with varying proportion of other
inflammatory cells.
Five cases in our study were subjected to open lung
biopsy. The histopathology report revealed variable degrees of
interstitial fibrosis, collagen deposition, thickened alveolar septa,
focal nests of proliferating fibro-blasts and interstitial inflammatory
infiltrate. In one case Pneumocystis carinii was found.
The analysis of readmission records revealed that 12
children had died, all of respiratory failure, with mean survival
duration of 2 years and 7 months after initial diagnosis. All the 4
children who had an acute presentation died within 3 months of
diagnosis.
Discussion
Chronic ILD in children is defined as the presence of
respiratory symptoms and/or diffuse infiltrates on chest radiographs,
abnormal pulmonary function tests with evidence of restrictive
ventilatory defect and/or impaired gas exchange, and persistence of any
of these findings for >3 months(5). Due to the lack of organized
reporting systems, determining the incidence or prevalence of ILD in
children is difficult. Indian studies on ILD have largely been limited
to adults(6,7) and studies in Indian children have been few(8).
Onset of symptoms in infancy in 7 cases (43.8%) might
suggest a possible genetic role. This young age of presentation has been
described in previous series(1,5,9). The chronic presentation of
symptoms in 12 cases (75%) was consistent with most other western
studies. The reason could be the fact that an acute presentation of ILD
is likely to be confused with a constellation of atypical pneumonias and
missed.
Bibasilar, dry, superficial, end inspiratory
crackles, usually described as "velcro crackles" were present in most
cases, compared to only 44% of the cases reported in the ERS task force
study(5). With advanced disease, clubbing of the fingers, cyanosis and
lymphadenopathy became evident. The usual end stage complications were
growth failure and pulmonary hypertension, noted in other studies
also(5,10).
The diagnostic value of serial chest X-rays in
our study, was comparable with the results of the National Jewish Center
study(1). ILD is usually suspected because of abnormal radiological lung
findings in spite of adequate antibiotic therapy including
antituberculous drugs (ATT). The endemic nature of tuberculosis, its
varied presentation, contact with an adult tuberculosis patient and
persistent clinical and radiological features in spite of antibiotics,
are the common reasons necessitating ATT in such children.
HRCT is useful, especially with a normal or
nonspecific chest X-ray, when there is a strong clinical
suspicion of ILD and this has been shown by positive HRCT findings in
the four children in whom serial X-rays did not reveal ILD. In
our study, HRCT was suggestive of ILD in 86.6% of the cases compared to
66% in a study by Copley, et al.(11). Ground glass opacification
was the commonest abnormality seen, an observation consistent with most
other studies(5,12,13). Honeycombing on a background of wide-spread
ground glass attenuation was present in three cases. Copley, et al.
had also reported three cases of nonspecific interstitial pneumonia, a
subset of idiopathic pulmonary fibrosis, with similar HRCT features(12).
BAL is the collection of airway lining fluid through
fibreoptic bronchoscopy and has been regarded as the "Liquid biopsy" of
the lung. Predominance of neutrophils, as seen in the BAL analysis of
our patients, is a finding associated with idiopathic pulmonary fibrosis
(14,15). In none of the cases the specific etiology of ILD was arrived
at.
Lung biopsy is considered the cornerstone of
diagnosis of ILD. Convincing the patient for lung biopsy proved to be a
major hurdle, as did the critical nature of illness, which made biopsy
impossible in few other cases. The five cases where open lung biopsy was
done showed histopathological features of idiopathic pulmonary
fibrosis. A specific diagnosis in accordance with the standard
classification of ILD was not forthcoming in any case.
All cases were started on steroids and tapering was
done as per response. The four cases, with an acute presentation,
deteriorated fatally within 3 months of presentation, suggesting acute
interstitial pneumonitis (Hamman Rich syndrome).
In conclusion, a systematic approach with clinical
examination, serial X-rays, HRCT and BAL, is helpful in the
diagnosis of pediatric ILD since lung biopsy is often not possible. The
retrospective nature of our study is a limitation as is the small study
population. Since no single pediatric center can see large numbers of
pediatric ILD patients, multicenter collaboration will be required to
extend these observations.
Contributors: DV has conceptualized the study and
collected the data. SG was involved in data analysis, outcome
assessment, literature review and writing the manuscript. NCG, KN, MS
were involved in the critical analysis of the manuscript.
Funding: None.
Competing interests: None stated.
|
Key Messages |
|
• Diagnosis of ILD requires a
high index of suspicion, as the clinical presentation is subtle,
variable, nonspecific and is likely to be confused with other
pneumonias.
• Progressive nature of the illness, clinical
findings, serial chest skiagrams, HRCT and BAL will be helpful
in the diagnosis of ILD, in the absence of lung biopsy.
|
