Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), encompasses over 150 heterogeneous conditions marked by chronic inflammation and progressive pulmonary fibrosis affecting the alveolar septa, airways, and microvasculature. These pathological changes compromise gas exchange, leading to exertional dyspnea, restrictive ventilatory impairment, reduced exercise capacity, and progressive respiratory failure. While global registries indicate that Idiopathic Pulmonary Fibrosis (IPF) accounts for the largest proportion of ILDs in Western countries, developing nations exhibit distinct epidemiological profiles. Studies across India report a substantial burden of Hypersensitivity Pneumonitis (HP) and Connective Tissue Disease-Associated ILD (CTD-ILD), influenced by environmental exposures, biomass fuel usage, and agricultural activities. Exclusion of infectious mimics, such as tuberculosis and fungal pneumonias, is essential in endemic regions. Furthermore, acute exacerbations of ILD (AE-ILD) are major drivers of morbidity and mortality. Identifying microbiological pathogens and cellular signatures in bronchoalveolar lavage (BAL) fluid during acute exacerbations is critical to guide targeted therapy. This study evaluates the clinical features, risk factors, HRCT imaging patterns, and microbiological profiles of patients presenting with ILD at a tertiary care center in Southern Odisha.

Study Design and Setting A cross-sectional observational study was conducted in the Department of Respiratory Medicine at M.K.C.G. Medical College and Hospital, Berhampur, Odisha (Latitude 19.3076°N, Longitude 84.8110°E) between February 1, 2024, and December 31, 2025. Institutional Ethics Committee approval was obtained prior to study initiation (Approval No. EC/NEW/INST/2022/2934). Study Population and Sample Size The study population comprised adult patients ( years) diagnosed with ILD based on clinical criteria and thin-section High-Resolution Computed Tomography (HRCT) of the chest. The minimum sample size of 88 patients was calculated using , assuming a confidence level, absolute precision, estimated prevalence, and accounting for a non-response rate. Inclusion Criteria Patients aged years diagnosed with ILD who provided written informed consent, including those with stable comorbidities (e.g., diabetes mellitus, hypertension, renal impairment). Exclusion Criteria Patients years, pregnant women, non-consenting individuals, and patients with active pulmonary tuberculosis or thoracic malignancies. Diagnostic Evaluation 1. Clinical Assessment: Detailed occupational, environmental, drug, smoking, and medical histories were documented alongside physical examination findings. 2. Imaging: HRCT scans ( slice thickness) were categorized into Usual Interstitial Pneumonia (UIP), probable UIP, Nonspecific Interstitial Pneumonia (NSIP), Organizing Pneumonia (OP), Hypersensitivity Pneumonitis (HP), or indeterminate patterns according to ATS/ERS/Fleischner Society guidelines. 3. Physiological Testing: Standard spirometry (measuring FVC, FEV1, FEV1/FVC) and the Six-Minute Walk Test (6MWT) were performed to assess functional impairment and exertional oxygen desaturation. 4. Laboratory and Serological Testing: Routine hematology, biochemistry, antinuclear antibodies (ANA), anti-CCP, rheumatoid factor (RF), anti-Scl-70, anti-U1RNP, and anti-Ku antibodies were evaluated. 5. Microbiological and BAL Analysis: Flexible bronchoscopy with BAL was performed when clinically indicated or during acute exacerbations (35 patients). BAL fluid underwent cytological differential counts, Gram staining, acid-fast bacilli (AFB) staining, bacterial cultures, and fungal testing. Statistical Analysis Continuous parameters are expressed as mean standard deviation (). Categorical variables are summarized as frequencies and percentages. Associations between clinical variables, risk factors, and disease subtypes were evaluated using crude Odds Ratios (OR) with Confidence Intervals (CI), Chi-square tests, or Fisher's exact tests. Statistical significance was set at

The cohort comprised 88 patients, including 50 females (56.8%) and 38 males (43.2%). Mean age was 53.5±13.5 years (range: 24–85 years). Table 1: Demographic and Occupational Profile of the Study Cohort (N=88) Parameter Category Number of Cases (n) Percentage (%) Gender Female 50 56.8% Male 38 43.2% Age Distribution <30 years 2 2.3% 31–50 years 41 46.6% 51–70 years 36 40.9% >70 years 9 10.2% Primary Occupation Housewife 46 52.3% Farmer 15 17.0% Laborer 8 9.1% Teacher 5 5.7% Factory/Industrial Worker 4 4.5% Others 10 11.4% Description: Table 1 details the demographic breakdown and occupational background of the 88 ILD patients. Females constituted the majority of the cohort, with the primary overall age cluster situated between 31 and 50 years. Non-industrial and agricultural occupations predominated, led by housewives (52.3%) and farmers (17.0%). Table 2: Clinical Symptoms, Physical Signs, and Comorbidities (N=88) Category Clinical Parameter Number of Cases (n) Percentage (%) Symptoms Shortness of Breath (Dyspnea) 68 77.3% Dry Cough 41 46.6% Gastroesophageal Reflux (GERD) 36 40.9% Bilateral Limb Swelling 32 36.4% Fever 18 20.5% Weight Loss / Anorexia 17 19.3% Skin Lesions 11 12.5% Joint Pain 6 6.8% Physical Signs Fine End-Inspiratory Crepitations 63 71.6% Digital Clubbing 36 40.9% Pedal Edema 32 36.4% Raised Jugular Venous Pressure 26 29.5% Comorbidities Hypertension 16 18.2% Diabetes Mellitus 14 15.9% Hypothyroidism 2 2.3% Description: Table 2 lists the presenting symptoms, physical examination findings, and co-existing medical conditions. Progressive exertional dyspnea (77.3%) and non-productive cough (46.6%) were the most prevalent symptoms. Fine "Velcro-like" end-inspiratory crackles represented the dominant physical finding (71.6%), followed by digital clubbing (40.9%). Table 3: Spirometric Function, 6MWT Distance, and HRCT Diagnostic Subtypes (N=88) Diagnostic Modality Parameter / Subtype Number of Cases (n) Percentage (%) Spirometry Pattern Restrictive Pattern 70 79.5% Normal Spirometry 18 20.5% FVC % Predicted FVC <34% 16 18.2% 34%≤"FVC"<50% 15 17.0% 50%≤"FVC"<60% 14 15.9% 60%≤"FVC"<70% 19 21.6% "FVC"≥70% 24 27.3% 6MWT Distance 180"-" 280" m" 37 42.0% 281"-" 380" m" 38 43.2% >380" m" 13 14.8% HRCT Pattern Reticulation 58 65.9% Traction Bronchiectasis 43 48.9% Honeycombing 40 45.5% Septal Thickening 32 36.4% Ground-Glass Opacities 20 22.7% Final Etiological ILD Subtype Idiopathic Pulmonary Fibrosis (IPF) 40 45.5% Connective Tissue Disease ILD (CTD-ILD) 28 31.8% Nonspecific Interstitial Pneumonia (NSIP) 8 9.1% Chronic Hypersensitivity Pneumonitis (HP) 6 6.8% Cryptogenic Organizing Pneumonia (COP) 4 4.5% Hermansky–Pudlak Syndrome (HPS) 2 2.3% Description: Table 3 summarizes physiological parameters, exercise tolerance, and radiological classifications. A restrictive defect was evident in 79.5% of patients. HRCT imaging demonstrated reticulation (65.9%), traction bronchiectasis (48.9%), and honeycombing (45.5%) as primary features, with IPF (45.5%) and CTD-ILD (31.8%) forming the main etiological classifications. Table 4: Microbiological and Cytological Profile of BAL Fluid in Acute Exacerbation (n=35) BAL Parameter Organism / Cytology Pattern Number of Cases (n) Percentage (%) Microbial Growth Sterile / No Growth 18 51.4% Klebsiella pneumoniae 8 22.9% Pseudomonas aeruginosa 5 14.3% Escherichia coli 3 8.6% Acinetobacter species 1 2.9% BAL Cytology Neutrophil-Predominant Pattern (>3% neutrophils) 14 40.0% Lymphocyte-Predominant Pattern (>15% lymphocytes) 12 34.3% Mixed Cellular Pattern 9 25.7% Description: Table 4 outlines bronchoalveolar lavage fluid findings from 35 patients evaluated during acute exacerbation. Cultures yielded bacterial pathogens in 48.6% of cases, with Klebsiella pneumoniae (22.9%) being the most common isolate. Cytological evaluation demonstrated a neutrophil-predominant profile in 40.0% of samples. Table 5: Statistically Significant Associations with IPF Subtype and UIP Pattern Evaluated Variable Factor Presence IPF Group (n=40) Non-IPF Group (n=48) Odds Ratio (95% CI) p-value Significance Smoking History Yes / No 16 / 24 5 / 43 5.7 (1.8–18.5) 0.0012 Statistically Significant GERD Symptoms Yes / No 26 / 14 10 / 38 7.1 (2.7–18.9) 0.00003 Highly Significant Variable Factor Presence UIP Pattern (n=49) Non-UIP Pattern (n=39) Odds Ratio (95% CI) p-value Significance Shortness of Breath Yes / No 45 / 4 23 / 16 7.8 (2.4–25.3) 0.00026 Highly Significant Digital Clubbing Yes / No 28 / 21 8 / 31 5.2 (2.0–13.9) 0.0005 Highly Significant Restrictive Spirometry Yes / No 46 / 3 24 / 15 9.6 (2.4–37.9) 0.000187 Highly Significant Description: Table 5 highlights statistical comparisons across disease categories. History of smoking (p=0.0012) and GERD (p=0.00003) demonstrated statistically significant associations with IPF. Similarly, patients exhibiting a UIP pattern on HRCT showed significantly higher odds of presenting with severe dyspnea, digital clubbing, and restrictive spirometric defects (p<0.001).

This study evaluated 88 patients with interstitial lung disease in Southern Odisha. The mean age of 53.5±13.5 years and female predominance (56.8%) align with Indian studies by Rai et al., Jafri et al., and Shreeswathy et al.. The female majority is largely attributable to the high prevalence of Connective Tissue Disease-Associated ILD (CTD-ILD), particularly Systemic Sclerosis (46.4% of CTD cases). Conversely, males predominated in the older age brackets (≥55 years) and presented more frequently with IPF, consistent with known sex-specific risk profiles. Progressive exertional dyspnea (77.3%) and dry cough (46.6%) were the most common presenting complaints, while fine end-inspiratory "Velcro" crackles (71.6%) and digital clubbing (40.9%) formed the primary physical signs. These findings mirror established clinical cohorts. Spirometric evaluation confirmed restrictive ventilatory defects in 79.5% of subjects, with 85.2% achieving <380" meters" on the 6MWT, reflecting functional exercise impairment. Etiologically, IPF represented the largest single group (45.5%), followed by CTD-ILD (31.8%). The predominance of IPF and CTD-ILD aligns with clinical studies by Rai et al. and Patel et al., though it differs from the national ILD-India registry where Hypersensitivity Pneumonitis was reported as the primary subtype. This variance likely stems from differences in regional occupational patterns, environmental exposure evaluation, and access to autoimmune serological screening. Statistical analysis demonstrated significant associations between IPF and both cigarette smoking ("OR"=5.7,p=0.0012) and GERD ("OR"=7.1,p=0.00003). Microscopic aspiration secondary to reflux is a recognized driver of ongoing alveolar epithelial injury and fibrotic remodeling. Patients exhibiting a UIP pattern on HRCT presented with higher odds of severe dyspnea ("OR"=7.8), clubbing ("OR"=5.2), and restrictive lung function ("OR"=9.6), supporting the link between structural honeycombing and physiological impairment. Microbiological evaluation of BAL fluid during acute exacerbations revealed bacterial growth in 48.6% of patients, with Klebsiella pneumoniae (22.9%) and Pseudomonas aeruginosa (14.3%) as the predominant isolates. Secondary bacterial infection can trigger acute functional decline in fibrotic lungs, emphasizing the role of BAL cultures during acute exacerbations. Cytological analysis showed a neutrophil-predominant pattern in 40.0% of exacerbation cases, reflecting active inflammation superimposed on underlying fibrosis.

IPF and CTD-ILD constitute the major proportion of interstitial lung disease cases in Southern Odisha. High-Resolution Computed Tomography remains the core imaging modality for identifying UIP and non-UIP patterns, reducing the need for invasive surgical lung biopsies. Smoking and GERD show significant associations with IPF development. Furthermore, secondary bacterial pathogens contribute to acute exacerbation episodes, highlighting the value of targeted bronchoalveolar lavage evaluation to guide therapeutic management.

1. Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, editors. Fishman’s Pulmonary Diseases and Disorders. 6th ed. New York: McGraw-Hill Education; 2023. 2. King TE Jr. Interstitial lung disease: a historical note. In: King TE Jr, editor. Clinical Atlas of Interstitial Lung Disease. New York: McGraw-Hill Education; 2018. p. 1–6. 3. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–748. 4. Kaunisto J, Salomaa ER, Hodgson U, Kaarteenaho R. Epidemiology of interstitial lung diseases in Finland. Am J Respir Crit Care Med. 2019;199(6):711–719. 5. Raghu G, Chen SY, Yeh WS, Maroni B, Li Q, Lee YC, et al. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults aged 18–64 years. Am J Respir Crit Care Med. 2014;189(8):1003–1009. 6. Singh S, Collins BF, Sharma BB, Joshi JM, Talwar D, Katiyar S, et al. Interstitial lung disease in India: results of a prospective registry. PLoS One. 2020;15(3):e0230218. 7. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44–e68. 8. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2020;202(3):e36–e69. 9. Meyer KC, Raghu G, Baughman RP, et al. The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2012;185(9):1004–1014. 10. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Rheumatol. 2024;76(8):1051–1069. 11. Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis: an international working group report. Am J Respir Crit Care Med. 2016;194(3):265–275. 12. Rai DK, Kumar A, Kumar S, et al. Clinical profile of interstitial lung disease at a tertiary care centre in India. Indian J Chest Dis Allied Sci. 2021;63(1):23–28. 13. Jafri S, Ahmed N, Saifullah N, Musheer M. Epidemiology and clinico-radiological features of interstitial lung diseases. Pak J Med Sci. 2020;36(3):365–370. 14. Shreeswathy M, Sunitha D, Veena V, et al. A study on the clinical and radiological profile of patients with interstitial lung disease in a tertiary care hospital. J Contemp Clin Pract. 2025;11(5):908–913. 15. Choradia PL, et al. Microbiological profile in acute deterioration of interstitial lung diseases. J Assoc Physicians India. 2022;70(4):45–50