Clinical Profile of Cystic Fibrosis in India: A Multi‐Centric Prospective Study

ABSTRACT

Background

Cystic fibrosis (CF) is considered to be extremely rare in India, but over the past few decades, multiple reports suggest that CF occurs in India and clinical features may be different. Reports on clinical features are limited to case series. In this multisite nationwide prospective study, we report the clinical profile of CF in Indian children.

Methods

Children below 18 years of age presenting with suggestive symptoms were enrolled at all the sites using a uniform protocol over a 5‐year period at four sites across India. Diagnosis of CF was based on either elevated sweat chloride levels or the presence of two pathogenic CF‐causing mutations, together with a clinical phenotype suggestive of the disease. Data collection included demographic, clinical, laboratory profiles, results of the aquagenic wrinkling test and overall outcomes of children diagnosed with CF.

Results

A total of 811 children were enrolled and 313 were diagnosed as CF during the study period. The median age at symptom onset and diagnosis was 2.25 months and 2.58 years, respectively. The common presenting symptoms included chronic cough (280, 89.5%), poor growth (213, 76.9%) and chronic diarrhoea (195, 62.3%). At the time of diagnosis, bronchiectasis on chest CT was present in 233 (90%) patients. Airway cultures grew Pseudomonas aeruginosa in 63 (36.8%), and Staphylococcus aureus in 32 (18.7%) patients. The common mutation was delta F508del, present in 31.3% of patients.

Conclusion

CF is prevalent across all the geographic regions of India. Delay in diagnosis remains a significant challenge and contributes to the development of severe complications.

Summary

• What is known

  • ○
    Cystic fibrosis is increasingly being recognised and reported across various regions of India.
• What is new

  • ○
    This is the first pan‐India study aimed at evaluating the clinical profile of cystic fibrosis amongst the diverse and heterogeneous Indian population.

1. Introduction

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of chromosome 7 [1]. The disease is characterised by abnormal ion transport across epithelial surfaces, resulting in thick, viscous secretions affecting multiple organs, particularly the respiratory and gastrointestinal system. The common clinical manifestations include chronic or recurrent respiratory infections, pancreatic insufficiency, malabsorption and failure to thrive [2]. CF was previously considered a rare disease in India. The first case report from India was published in 1968 [3]. Subsequent studies have demonstrated the presence of this disease across diverse geographic and ethnic populations of the country [4, 5]. However, unlike many developed countries where CF has been extensively studied and well‐characterised, data from India remain limited and are largely restricted to small case series. To address this gap, we conducted a Pan‐India study involving four major tertiary care centres, which are located in different geographic regions of the country. This study was designed as a prospective multi‐centric observational study with evaluation of the clinical phenotype at the time of diagnosis. Prior to initiation of the study, structured CF services were not uniformly available across participating centres. As part of the study framework, dedicated CF clinics were established at each site, enabling consecutive enrolment of newly diagnosed patients during the study period. All enrolled patients were evaluated using a standardised protocol to systematically capture various clinical details from the enrolled patients. Prospective enrolment ensured uniform clinical evaluation and minimised missing or incomplete data commonly encountered in retrospective studies. The objective of this multi‐centric study was to describe the clinical profile of children with cystic fibrosis across geographically diverse regions of India.

2. Material and Methods

This multisite cohort study was conducted across four geographical regions of India over a 5‐year period, from 2019 to 2024 at four university hospitals, including All India Institute of Medial Sciences (AIIMS) New Delhi, Sher‐i‐Kashmir Institute of Medical Sciences (SKIMS) Srinagar, All India Institute of Medial Sciences (AIIMS) Jodhpur and Christian Medical College (CMC) Vellore. Children under 18 years of age presenting to paediatric outpatient services with recurrent or persistent pneumonia, frequent bulky oily stools and/or failure to thrive were subjected to screening for CF. After obtaining written informed consent from parents or guardians, eligible children were enrolled. All enrolled patients underwent a sweat test using an indigenously developed and validated method [6] based on the principle of pilocarpine iontophoresis. Sweat chloride levels were estimated by the Schales and Schales method [7].

Children with sweat chloride levels > 60 mEq/L on two separate occasions and/or two pathogenic CF‐causing mutations were diagnosed with CF. Data for all newly diagnosed children during the study period including demographic profile, clinical details, various laboratory parameters and other relevant information were entered in a predesigned software programme and electronically transferred to the nodal centre (AIIMS New Delhi). In addition, a blood sample was collected for detailed CF mutation analysis.

All children diagnosed with CF were managed as per the protocol agreed upon by all participating sites. The treatment included airway clearance, pancreatic enzyme replacement therapy (PERT), nutritional support and inhaled antibiotics. DNase was used selectively, depending on the availability. CFTR modulators are currently not accessible in India, and none of the patients in our cohort received them.

The authors declare that the research presented in this manuscript adheres to the ethical principles outlined by the Institutional Ethics Committee (SKIMS) [RP 170/2018], Institutional Ethics Committee (AIIMS, New Delhi) [RP12/2018], Institutional Ethics Committee (AIIMS, Jodhpur) [AIIMS/IEC/2018/1641] and Institutional Ethics Committee (CMC, Vellore) [IRB‐11722/Dec 2018]. All procedures involving human participants were conducted in accordance with the ethical standards of India and the Declaration of Helsinki (1964), as revised in 2013.

2.1. Statistical Analysis

The data from all the sites were pooled together. For continuous variables, mean ± SD and median with IQR were calculated. For discreet data, simple frequency was calculated. Differences in findings of different sites were calculated by Student's t‐test/Mann–Whitney U test and chi square test. Bivariate analysis was also performed to compare various variables between patients who survived and those who died during the study period. IBM SPSS statistical software (Armonk, NY: IBM Corp) was used for data analysis. No part of the content in this manuscript was created using any language learning model (such as ChatGPT). Only minor grammatical corrections were made with the assistance of a language model.

3. Results

In this multisite prospective study, a total of 1455 patients with suggestive symptoms were screened across all four study sites. Of these, 811 patients met the criteria for further evaluation for CF and 313 were confirmed as CF. 112 (35.78%) cases were from AIIMS Delhi, 91 (29.07%) from SKIMS Srinagar, 72 (23.03%) from CMC Vellore and 38 (12.1%) from AIIMS Jodhpur.

3.1. Demographic Profile

The place of origin of enrolled children suggested that they were nearly from all states and union territories of India, as well as from several neighbouring countries (Figure 1). Amongst neighbouring countries, the highest number of patients were enrolled from Bangladesh (17, 5.4%). Majority of patients were boys (196, 62.6%). Consanguinity was reported in 96 patients (30.7%), most frequently it was found in patients enrolled from J&K (43, 47.3%) followed by Tamil Nadu (26, 36.4%).

FIGURE 1.

Geographical distribution of enrolled patients with Cystic Fibrosis across India and neighbouring countries. The figure depicts a map of India and adjacent nations, illustrating the number of patients with Cystic Fibrosis enrolled from each Indian state and from neighbouring countries included in the study.

3.2. Clinical Features

Table 1 shows the Demographic and Clinical profile of the study population. A history of recurrent/persistent pneumonia was present in 213 (68.1%) patients, poor growth in 241 (77%) and foul‐smelling bulky stools in 116 (37.1%) patients. At presentation, the most common symptom was cough (280, 89.5%). A history of a salty‐tasting kiss was reported in 83 (26.5%) patients, including 35 (38.5%) from colder regions like Jammu and Kashmir and 13 (34.2%) from hotter regions such as Rajasthan. Other atypical manifestations included rectal prolapse in 25 (8%) patients and history of dehydration in 107 (34.1%) patients, with significantly higher frequency observed in patients from Rajasthan (24, 63.2%) compared to other sites. The median (IQR) age at onset of symptoms was 2.25 (1–6) months, and the median (IQR) age at diagnosis was 2.58 (0.64–8.0) years. The youngest patient diagnosed was less than 1 month old. The median (IQR) age at diagnosis was lowest in Rajasthan (1.55 [0.33–5.0] years) and highest in Tamil Nadu (3.87 [0.77–8.61] years). However, the difference was not statistically significant (p = 0.237). The median (IQR) Weight‐for‐age Z‐score was −2.86 (−3.98 to −1.65) and median (IQR) Height‐for‐age Z‐score was −2.0 (−3.26 to −0.79).

TABLE 1.

Demographic and clinical profile of the study population (N = 313).

Variable	Cumulative value	AIIMS New Delhi	CMC Vellore	AIIMS Jodhpur	SKIMS Srinagar	p
Male. No (%)	196 (62.6)	76 (67.9)	43 (60.6)	26 (68.4)	51 (56.0)	0.29
Female. No (%)	117 (37.4)	36 (32.1)	28(39.4)	12 (31.6)	40 (44)
Age at diagnosis in years. Median (IQR)	2.58 (0.64–8.0)	3 (0.7–8.0)	3.87 (0.7–8.6)	1.5 (0.3–5.0)	1.7 (0.7–8.0)	0.23
Age of onset of symptoms in months. Median (IQR)	2.25 (1–6)	2.5 (1–6)	3 (1–6)	2 (1–4)	2 (1–12)	0.84
Height for age Z‐score. Median (IQR)	−2.0 (−3.2, −0.79)	−2.1 (−3.3, −1.2)	−2.09 (−3.4, −0.75)	−2.1 (−3.2, −0.69)	−1.4 (−3.0, −0.30)	0.12
Weight for age Z‐score. Median (IQR)	−2.8 (−3.9, −1.6)	−3.0 (−4.1, −1.9)	−3.1 (−3.9, −1.9)	−3.5 (−5.1, −2.3)	−2.0 (−3.0, −1.1)	0.00
Recurrent/persistent cough. No (%)	280 (89.5)	104 (92.9)	57 (79.2)	33 (86.8)	86 (94.5)	0.07
Recurrent/persistent pneumonia. No (%)	213 (68.1)	75 (68.2)	33 (45.8)	30 (78.9)	75 (82.4)	0.00
Recurrent wheeze. No (%)	160 (151.1)	54 (48.2)	37 (51.4)	20 (52.6)	49 (53.8)	0.87
Poor growth. No (%)	241 (76.9)	89 (80.2)	53 (73.6)	35 (92.1)	64 (70.3)	0.04
Malabsorption. No (%)	195 (62.3)	64 (57.1)	42 (58.3)	29 (76.3)	60 (65.9)	0.142
Recurrent dehydration. No (%)	107 (34.1)	39 (34.8)	20 (27.8)	24 (63.2)	24 (26.7)	0.003
Salty kiss. No (%)	83 (26.5)	21 (18.9)	14 (19.4)	13 (34.2)	35 (38.5)	0.005
Salt craving. No (%)	30 (9.6)	9 (8.2)	2 (2.8)	4 (10.5)	15 (16.7)	0.026
Rectal prolapse. No (%)	25 (8.0)	14 (12.6)	8 (11.1)	3 (7.9)	0	0.007
Pancreatitis. No (%)	8 (2.6)	1 (2.8)	5 (6.9)	1 (2.6)	1 (1.1)	0.059
Recurrent abdominal pain No (%)	67 (21.4)	24 (21.6)	13 (18.1)	8 (21.1)	22 (24.2)	0.8
Neonatal jaundice. No (%)	26 (8.3)	14 (12.7)	7 (9.7)	3 (7.9)	2 (2.2)	0.062
Family H/O of sibling with CF. No (%)	40 (12.8)	14 (12.5)	5 (6.9)	7 (18.4)	14 (15.4)	0.25
Consanguinity. No (%)	90 (30.7)	18 (16.2)	26 (36.6)	9 (23.7)	43 (47.3)	0.00
Clubbing (N = 290)	141 (48.6)	54 (50.5)	24 (34.3)	20 (54.1)	43 (56.6)	0.04

3.3. Basic Investigations

Aquagenic wrinkling was performed in 287 patients, of whom 217 (75.6%) patients developed wrinkling within 3 min. The sensitivity of the test was 77.2% (78) at AIIMS New Delhi, 88.1% (59) at CMC Vellore, 80.0% (24) at AIIMS Jodhpur and 62.9% (56) at SKIMS Srinagar. There was a statistically significant difference in the frequency of wrinkling amongst different geographic locations of the country (p = 0.025). Clubbing, a marker of chronic lung disease, was seen in 141 (45%) patients.

Chest CT scan was done in 244 patients. Bronchiectasis was observed in 233 (90%) patients. It was diffuse in 10 (6%) patients, whilst in 223 (94%) patients, it variably involved different lobes of the lungs. At enrollment, 171/238 (71.8%) children showed growth of one or more microorganisms. Pseudomonas aeruginosa was the most frequently isolated organism (63, 36.8%), followed by Staphylococcus aureus (32, 18.7%). Of the 313 enrolled children, 21 (6.7%) had chronic P. aeruginosa infection and 12 (3.8%) children had chronic S. aureus infection. Burkholderia Cepacia was isolated in two children; a 6‐month old boy and a 12.5‐year‐old girl. Aspergillus fumigatus was isolated in two children. None of the patients had grown non‐tuberculous mycobacteria (NTM) in sputum or throat swab cultures. Allergic bronchopulmonary aspergillosis (ABPA) was not investigated. The detailed microbiological spectrum is reported separately [8]. Spirometry at diagnosis was performed in 42 (13.4%) children, with mean ± SD FEV1 predicted values of 63.4% ± 24.9%.

During the study period, we documented 28 (8.94%) deaths amongst enrolled patients across all sites. Children who died were comparatively younger. The median (IQR) age at death was 1.0 year (0.42–4.4). The youngest death occurred in a 45‐day‐old infant, whilst the oldest was a 21‐year‐old patient. All deceased children were malnourished, with median height‐for‐age and weight‐for‐age Z‐scores of −3.7 (IQR −2.06 to −5.33) and −4.17 (IQR −3.54 to −5.62), respectively. P. aeruginosa infection was present in 11 (39%) of these patients.

Bivariate analysis revealed that the median age was significantly lower amongst expired children (0.88 years [IQR 0.29–6.42]) compared to survivors (3.0 years [IQR 0.75–8.0]), p = 0.017. Median weight‐for‐age Z‐scores were significantly lower amongst expired children (−4.34 [IQR −5.69 to −3.61]) compared to survivors (−2.73 [IQR −3.79 to −1.47], p < 0.001). Similarly, height‐for‐age Z‐scores were significantly lower amongst expired children (−3.70 [IQR −5.23 to −2.04]) compared to survivors (−1.90 [IQR −3.03 to −0.66], p < 0.001). There was also a statistically significant association between sputum culture results and mortality ((χ ²) = 17.79, p = 0.003; Cramer's V = 0.24). Children who died had higher proportions of P. aeruginosa (28.6% vs. 21.1%) and S. aureus (17.9% vs. 10.2%) colonisation, whereas negative cultures were more frequent amongst survivors (56.8% vs. 32.1%).

3.4. Mutation Profile

Amongst 260 children (520 chromosomes), 105 CFTR variations were identified. The most common mutation, p.Phe508del, was present in 31.34% of alleles.

4. Discussion

A total of 313 children were diagnosed with CF across four sites over a 5‐year study period. Important findings include that the place of origin was spread all over the country, suggesting that CF occurs in all ethnic and geographic regions of India. The median age at diagnosis was 2.58 years (IQR 0.64–8.0), whereas the median age of symptom onset was 2.25 months (IQR 1–6), suggesting a significant delay in the diagnosis. Consanguinity was observed in 30% of the study population with particularly high prevalence in Jammu & Kashmir and Tamil Nadu. A significant proportion of affected children had severe malnutrition, advanced lung disease, as reflected by high rates of digital clubbing, reduced FEV1 and bronchiectasis. A significant proportion had P. aeruginosa infection at the time of diagnosis. Some regional variations were observed in clinical features, such as consanguinity and history of dehydration. Whilst the most common mutation identified was delta F508del, its allele frequency was 31.34%, considerably lower than that reported in White populations.

The reasons for delayed diagnosis of CF in India include limited awareness of CF clinical phenotypes amongst paediatricians, strong beliefs that CF does not occur in Indian children, non‐availability of diagnostic tests, and overlap of clinical symptoms with common morbidities like pneumonia, diarrhoea and malnutrition [4]. In this study the median age at diagnosis was 2.58 years (IQR 0.64–8.0). Reports from northern and western India also report delayed diagnosis with mean age at diagnosis as 24 and 32.5 months, respectively [8, 9]. These data suggest a significant delay compared with the mean age of 6 months reported in USA [10]. Several developing regions have demonstrated improvements in CF services over the last decade, resulting in a reduction in the age at diagnosis. Studies from Turkey and South Africa reported median ages at diagnosis of 1.7 years [11] and 7.6 months [12], respectively. These comparisons highlight the urgent need to raise awareness amongst paediatricians and primary care physicians in India to consider CF as a differential diagnosis and to promptly refer suspected cases to specialised centres for early diagnosis and intervention. The measures suggested to improve awareness amongst physicians include holding workshops of small groups by interactive case‐based discussion. Both sweat chloride testing and genetic analysis are available at limited centres in India; genetic tests are also cost‐prohibitive. To address this gap, data from the present study were used to develop the CF Clinical Diagnostic Score (CF‐CDS) [13], derived through stepwise logistic regression analysis. Independent predictors of CF included: a history of an affected sibling, digital clubbing, hyponatremia, metabolic alkalosis, stool fat globule positivity, P. aeruginosa isolation in sputum and aquagenic wrinkling within 3 min. The CF‐CDS demonstrated excellent diagnostic accuracy (AUROC 0.923, 95% CI: 0.899–0.946); at a cut‐off ≥ 2.5, the sensitivity and specificity were 87% and 81%, respectively [13].

Consanguinity was observed in 30% of the study population with some variation across study sites. The rate of consanguinity was highest in Jammu and Kashmir and Tamil Nadu compared with the north and western regions of the country, reflecting underlying sociocultural practises. Shastri et al. [14] reported a lower rate of consanguinity (13%) in their cohort from AIIMS New Delhi.

The common clinical features in our patients were chronic productive cough, recurrent pneumonia, failure to thrive and malabsorption; these features were similar to case series reported in White populations. However, our patients presented with more advanced disease, as indicated by severe malnutrition, digital clubbing, bronchiectasis and P. aeruginosa colonisation in sputum. The advanced stage at presentation is likely attributable to the lack of newborn screening (NBS) as well as inadequate CF care infrastructure in India, including limited diagnostic facilities, shortage of trained workforce, restricted access to essential medications, high treatment costs and challenges in ensuring regular follow‐up. Although enrolled subjects began clinical symptoms at a median age of 2.25 months, the diagnosis was delayed to 2.58 years. A similar clinical pattern has been described in the South African CF Registry [12] cohort. In contrast, children from industrialised nations are predominantly diagnosed in the neonatal period through NBS programs [10]. These patients subsequently undergo structured follow‐up protocols, have easy access to inhaled therapies (inhaled antibiotics and DNase), nutrient‐dense dietary support and are increasingly treated with highly effective CFTR modulator therapies. Consequently, the clinical phenotype of CF in these countries has shifted significantly, with affected children typically presenting with milder respiratory symptoms, preserved lung function, improved growth parameters and markedly improved survival outcomes [15].

During the study period, we documented 28 total deaths (8.94%) amongst enrolled patients. The majority were young children who presented with advanced respiratory disease and succumbed soon after diagnosis was made and appropriate management instituted. Severe malnutrition, as indicated by markedly low weight‐ and height‐for‐age Z‐scores, contributed significantly to poor outcomes. On bivariate analysis, younger age at presentation, severe malnutrition and P. aeruginosa infection were significantly associated with mortality. The median age at death was only 1 month; this emphasises the urgent need for earlier identification, to enable timely diagnosis and initiation of treatment.

Failure to thrive, defined as weight‐for‐age Z‐score < −2 SD was present in 213 (76.9%) children at presentation. This high prevalence is likely attributed to chronic pancreatic insufficiency leading to malabsorption, as well as recurrent or chronic cough, which increases the work of breathing and energy expenditure [16]. Growth failure has also been identified as a significant risk factor for the rapid deterioration of lung function in CF patients [17].

At the AIIMS Jodhpur site, a history of dehydration was observed in 63.2%, a proportion significantly higher than at other study sites. This finding may be attributable to the geographic and climatic conditions of the region, which is predominantly desert terrain in western India, where summer temperatures often exceed 45°C. Such extreme heat predisposes these children to be particularly susceptible to dehydration. Pseudo‐Bartter syndrome has been reported as an isolated abnormality in neonates with CF, who later manifest the full spectrum of disease symptoms [18].

Other symptoms noted included salty taste on kissing (83, 26.5%), salt craving (30, 9.6%) and rectal prolapse (25, 8%). These findings emphasise the need for a high index of suspicion especially when the patient has atypical CF manifestations.

Approximately 75% of enrolled children developed aquagenic wrinkling within 3 min, a clinical sign first described by Elliot et al. in 1974 [19]. Aquagenic wrinkling is a simple bedside test increasingly recognised in patients with CF. In the present study, regional variation in the frequency of aquagenic wrinkling was observed, with relatively lower prevalence at the SKIMS Srinagar site compared with other participating centres, all of which are situated in regions with warm climatic conditions. Although the underlying explanation remains uncertain, environmental factors such as ambient temperature, humidity and baseline skin hydration may influence eccrine gland function and electrolyte dynamics in the skin. Colder climatic regions, such as Srinagar, are generally associated with lower sweating and altered skin hydration, which could theoretically influence the osmotic response underlying aquagenic wrinkling. As assessments were performed by trained research nurses across multiple centres, some degree of inter‐observer variability cannot be excluded. However, interobserver variability was minimised through use of a standardised protocol across all sites, incorporating a fixed duration of water immersion and uniform interpretation criteria.

Aquagenic wrinkling at 3 min was included as one of the parameters in the CF Clinical Diagnostic Score (CF‐CDS) developed from this cohort [13]. Importantly, the diagnostic performance of the CF‐CDS reflects the combined contribution of multiple clinical and laboratory variables rather than reliance on a single subjective parameter. In resource‐limited settings, where access to sweat chloride estimation or genetic testing may be limited or delayed, simple bedside clinical indicators such as aquagenic wrinkling may provide useful supportive evidence to raise clinical suspicion of CF. Nevertheless, potential inter‐observer variability represents an important limitation, and future studies evaluating inter‐observer agreement using standardised training methods may further strengthen the reliability of this clinical sign.

The most common mutation seen in White populations, that is, delta F508del was detected in only 31% of alleles in our cohort. This supports existing evidence that the mutation profile of CF in India is highly heterogeneous. Although delta F508del remains the most common mutation, it is present in a substantially lower proportion of Indian children compared with Western populations [2, 20]. A recent study by Varkki et al. [21], conducted predominantly on a South Indian population, also found allele frequency of delta F508del (27%) considerably lower than that typically seen in European cohorts (around 70%).

The strengths of this multi‐centre study include the prospective multicentric design using a standardised evaluation protocol across geographically diverse regions of India. Prospective enrolment enabled systematic and uniform documentation of clinical features, laboratory parameters and microbiological findings at the time of diagnosis, thereby minimising missing data and recall bias commonly encountered in retrospective studies.

The limitations of this study are that, first, it might not be fully representative of all CF patients in India, as only four centres were included, and India is a very large country with the highest population in the world. The second limitation of our study is that we could not ascertain the exact cause of death, as no autopsies were performed on the children who died during the study period. Data regarding the proportion of patients presenting with atypical manifestations such as electrolyte imbalance, rectal prolapse or neonatal cholestasis as the initial presentation of CF were not systematically captured; this also represents a limitation of the study.

5. Conclusions

This study demonstrated that CF occurs across diverse geographic regions of India. However, a significant delay in diagnosis remains a major challenge, resulting in advanced disease at presentation. Chronic respiratory symptoms, failure to thrive, and chronic diarrhoea were the most common clinical manifestations across study sites. Young infants with severe malnutrition and P. aeruginosa infection were at increased risk of mortality. The allele frequency of the common mutation delta F508del was substantially lower than that reported in White populations, highlighting the genetic heterogeneity of CF in India. These findings have important clinical and public health implications. The relatively low prevalence of delta F508del compared with Western populations suggests the need for development of region‐specific CFTR mutation panels tailored to the Indian population. A targeted gene panel based on the mutation spectrum identified in Indian patients may improve diagnostic yield whilst reducing the cost of genetic testing, thereby enhancing accessibility of molecular confirmation in resource‐limited settings. The substantial delay between onset of symptoms and diagnosis observed in this cohort highlights the need to improve awareness of CF amongst paediatricians and primary care physicians. Integration of CF evaluation into routine paediatric assessment of children presenting with recurrent pneumonia, persistent cough, failure to thrive, chronic diarrhoea, electrolyte imbalance or pseudo‐Bartter syndrome may facilitate earlier recognition and timely referral for confirmatory testing. The CF‐CDS derived from this study may serve as a practical screening tool to support early identification of suspected cases, particularly in settings where access to sweat chloride estimation or genetic testing may be limited.

Author Contributions

P.K., J.P.G., J.I.B., N.D., S.V., K.R.J., R.L. and S.K.K.: involved in development of protocol, execution of study, and preparation of initial draught. A.K., I.K., J.S., M.K., M.K., M.R.C., N.G., P.M., R.G. and P.B.: involved in data collection, management of children and preparation of initial draught. All the authors critically reviewed the final version of the manuscript. S.K.K. will act as a guarantor for this manuscript.

Funding

Indian Council of Medical Research (ICMR): RFC no. RBMH/CAR/1/2018–2019 dated 27/07/2018.

Ethics Statement

The individual institutional ethical committees approved this study.

Consent

It was taken for all patients at individual sites.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.