In this retrospective chart review, records of children with CLM, attending the pediatric chest clinic of a tertiary care center in India, from 2009 to 2019, were evaluated. Congenital lung malformations had been diagnosed based on clinical features, chest X-ray (CXR), Contrast enhanced computed tomography (CECT) of chest, and histopathology, if resection was done. Information on demographic profile, anthropometry, respiratory system symptoms, chest imaging, spirometry, hospitalizations, treatment, timing of surgical intervention, associated reactive airway disease and follow-up including final outcome was retrieved. Data regarding echocardio-graphy, barium swallow, nuclear scan or bronchoscopy, wherever available, were also noted. Those who did not attend our clinic after first visit were considered as lost to follow-up. These children were contacted telephonically and any missing data were obtained. This study included the CLMs, namely, congenital small lung (agenesis, aplasia and hypoplasia) and congenital thoracic mal-formations (CPAM), sequestration, bronchogenic cyst, foregut cyst) [7]. We excluded congenital airway malformations and congenital diaphragmatic hernia. Congenital small lung was diagnosed based on clinical signs of volume loss on particular side, CECT chest showing low lung volume with ipsilateral small pulmonary artery and bronchial hypoplasia/aplasia if bronchoscopy was performed. Differential diagnoses considered were lung collapse secondary to impacted mucous plug/foreign body or external airway compression. Bronchogenic cyst was diagnosed based on clinical signs, smooth bordered spherical mass, associated vertebral abnormalities on CECT chest and histopathology after surgical resection. Differential diagnoses for cystic lesions considered were lung abscess, hydatid cyst, fungal disease, tuberculosis, infected bullae, vascular malformations and neoplasm based on the clinical symptoms and investigations. Congenital lobar emphysema (CLE) was diagnosed based on signs of hyper-inflation of particular lobe after exclusion of intraluminal/extra luminal compression by CECT chest or bronchoscopy. Differential diagnoses for CLE considered were pneumothorax, foreign body bronchus/external compression of bronchus causing ball-valve mechanism leading to air entrapment. CPAM was diagnosed on solid/cystic mass lesion on CECT and later histopathology. Differential diagnoses for CPAM considered were necrotizing pneumonia, sequestration, congenital diaphragmatic hernia, and peripherally located bronchogenic cyst [7]. Institute ethics committee approved the study protocol with waiver of consent.

Statistical analyses: Data were entered in MS Excel and analyzed using STATA ver.12 (Stata Corp). Significance of difference among various groups were compared using Student t-test (uniformly distributed continuous data), Mann-Whitney test (skewed data) or Chi square test or Fisher exact test (for categorical data) as applicable. Statistical significance was set at P value of <0.05.

Sixty-three children with congenital lung malformations were registered during study period and 48 case records could be retrieved. Major malformations were congenital lung hypoplasia 24 (50%), cystic pulmonary airway malformation 9 (19%), bronchogenic/foregut cyst 8 (17%) and congenital lobar emphysema 4 (8%). Baseline characteristics of enrolled children are shown in Table I.

The children with congenital small lung included right hypoplasia (n=6), right agenesis (n=5), left hypoplasia (n=9), left aplasia (n=2), and left agenesis (n=2). Of these, 3 children (13%) were treated as tuberculosis at other medical centers, prior to diagnosis, 7 (29%) were receiving cotrimoxazole prophylaxis and 17 (71%) children were advised pneumococcal and annual influenza vaccines. Two children with congenital small lung underwent pneumonectomy for repeated infections and associated lung sequestration, respectively. One child with right lung hypoplasia had systemic blood supply to the lung, which was coil embolized electively. None of the children with congenital small lung were on home oxygen. Thirteen children with congenital small lung underwent echocardiography and findings included dextrocardia-3, ventricular septal defect-2, tetralogy of fallot-1, atrial septal defect-2, patent ductus arteriosus-2, patent foramen ovale-1, pulmonary arterial hypertension-1 and normal echocardiography-2. One child had horse-shoe lung. Median (IQR) number of hospitalizations during follow-up over 19 months were significantly less than that prior to diagnosis 0 (0,0) vs1 (0,2) (P=0.001). Median (IQR) weight z score at diagnosis were than at follow-up [-2.4 (-3.4, -2.4) vs -1.7 (-2.6, -0.18), P=0.13].

Four children had bronchogenic cysts and another four had foregut duplication cysts. The hospitalization rate in follow up had significantly reduced from that prior to cyst removal, 0.5 (0,1) vs 4 (2,6) (P=0.02), respectively. Two children were treated as tuberculosis prior to referral. One of four children with foregut duplication cyst had features suggestive of gastric mucosa on nuclear scintigraphy study.

There were 9 children with CPAM (left lower lobe-3, right lower lobe-2, right upper lobe-2, left upper lobe-2). Median (IQR) number of hospitalizations before and after surgical resection were 1(1,1) vs 0(0,0), respectively (P=0.016).

Right lower lobe pulmonary arteriovenous malformation was diagnosed in a child, 60 months old, who underwent coil embolization 2 months later. Another child with Scimitar syndrome, underwent right lung pneumonectomy at 4 months of age. Table II depicts demography, clinical features and outcomes of major congenital lung malformations. All children presenting with CLM were symptomatic with almost half of them having associated reactive airway disease, receiving inhaled corticosteroids and 10% being treated as tuberculosis.

In our center, lung hypoplasia was found to be the most common CLM, followed by cystic pulmonary airway malformation (19%), bronchogenic/foregut duplication cysts (17%), and congenital lobar emphysema (8%). Around 60% of non-lung hypoplasia CLMs were operated at a median age of 14 months. Lung hypoplasia was the most common CLM to be associated with congenital heart disease. Almost half of children had concurrent reactive airway disease. Hospitalization rate for respiratory problems were significantly decreased after diagnosis and supportive management or surgical resection, whichever was applicable.

The high proportion of lung hypoplasia among all lung malformations may be due to referral bias for surgical intervention to pediatric surgery clinic. Lung hypoplasia is known to be associated with other lung malformations such as cystic adenoid malformations, congenital diaphragmatic hernia, pleural effusions etc. [4,5]. In our cohort, one each had associated horse-shoe lung and intra-lobar sequestration, respectively. Though hemoptysis is rarely reported in lung hypoplasia/agenesis [6], 2 children in our cohort had hemoptysis, with one of them requiring coil embolization for the same. The significant decline in hospitalization rate post enrolment in our clinic, was attributed to regular follow up, nutritional and immunization counseling, regular cotrimoxazole prophylaxis and vaccination against pneumococcus and influenza in addition to routine vaccination,

Unlike reports from other parts of the world, where CPAM was reported as the most common lung malfor-mation [7-9), this pattern was not seen in our cohort, probably due to referral bias. The median age of diagnosis of CLM and its surgical intervention was relatively higher (24 months) in our cohort, compared to other reports [7,9-12] thus revealing the low awareness level among clinicians regarding CLMs. Further, in contrast to those cohorts [9,11], not a single child was asymptomatic at the time of presentation to our centre, highlighting the poor antenatal screening programs for lung malformations. Similar to previous reports [8,12], majority of children had associated hyper-reactive airway disease in our cohort. Our data shows that nearly 10% of the children were being treated empirically as pulmonary tuberculosis, prior to referral, underscoring the fact that persistent imaging abnormalities are often misdiagnosed in endemic countries.

The strength of this study is in its data from large numbers of children, along with a reasonable follow-up, unlike previously published data from India. Further the study brings out the limitations in diagnosing, treating and follow up of such children in lower middle income countries. The limitations of the study is it’s retrospective design, substantial loss to follow up (18%), non-availability of data on pulmonary function tests and absence of assessment of chest wall deformities.

Lung hypoplasia was the most common congenital lung malformation referred to a tertiary care pediatric pulmonology centre with almost none having been detected in the antenatal period. Age of diagnosis and surgical intervention was often delayed. Reactive airway disease was the most common associated respiratory morbidity. Further studies regarding follow-up of such children are required, from developing countries.

Ethics clearance: 　Institute Ethics Committee; Ref No. IEC-770/08.11.2019; RP- 10/2019, dated 27 November, 2019

Contributors: All authors were involved in patient management, reviewed the manuscript, and approved the final version of manuscript.

Funding: None; Competing interest: None stated.

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