Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fibrosing interstitial lung disease (ILD) of unknown etiology that predominantly affects older adults. It is characterized by irreversible architectural distortion and a poor prognosis, with median survival ranging from 3 to 5 years post-diagnosis [1]. In recent years, awareness and diagnosis of IPF have increased in India, with studies estimating a growing national burden of ILDs, including IPF, likely due to both environmental and genetic factors [2]. Patients with IPF frequently present with comorbidities such as hypertension, diabetes, gastroesophageal reflux disease, and cardiovascular conditions [3]. Of particular interest is the growing recognition of Obstructive Sleep Apnoea (OSA) as a common yet underdiagnosed comorbidity in IPF. OSA is defined by repetitive episodes of upper airway obstruction during sleep, resulting in intermittent hypoxia and sleep fragmentation [4]. It is highly prevalent in the general population, affecting nearly one billion individuals globally [5]. The coexistence of IPF and OSA is clinically significant. The presence of OSA in IPF has been associated with worsened nocturnal hypoxemia, increased pulmonary artery pressures, reduced quality of life, and potentially more rapid disease progression [6]. Despite these risks, screening for OSA is not routinely incorporated into the standard evaluation of IPF patients, particularly in resource-limited settings like India. Previous studies have reported OSA prevalence rates between 59% and 88% among IPF patients, underscoring the need for early identification and management of this comorbidity [7]. However, there is a paucity of Indian data examining the prevalence, severity, and clinical correlates of OSA in this population. The present study was undertaken to evaluate the prevalence of OSA in patients with IPF, and to explore its association with clinical symptoms, comorbidities, pulmonary function, and polysomnographic parameters in a tertiary care setting. OBJECTIVES Primary Objective: • To evaluate the prevalence of Obstructive Sleep Apnoea (OSA) among patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF) in a tertiary care setting. Secondary Objectives: • To assess the clinical and demographic factors associated with OSA in IPF. • To examine the relationship between OSA and pulmonary function parameters, particularly forced vital capacity (FVC) and arterial blood gases. • To evaluate polysomnographic findings in IPF patients with OSA. • To explore associations between OSA severity and anthropometric measurements, such as body mass index (BMI) and neck circumference.

Study Design and Setting This was a hospital-based, observational descriptive study with a prospective design, conducted in the SCLI ward of the Department of Respiratory Medicine, Medical College and Hospital, Kolkata. Study Duration Data were collected over an 18-month period, from November 1, 2022, to April 30, 2024. Study Population The study included all patients admitted with Idiopathic Pulmonary Fibrosis (IPF) during the study period who met the inclusion criteria. Inclusion Criteria • Age ≥ 18 years • Stable dyspnoea • High-resolution computed tomography (HRCT) findings consistent with Usual Interstitial Pneumonia (UIP) or probable UIP, as per ATS 2022 criteria • No alternative diagnosis Exclusion Criteria • Diagnosed neurological or psychiatric illness • Total sleep time < 4 hours on polysomnography • Other chronic pulmonary diseases (excluding ILD) • Current use of medications affecting sleep architecture (e.g., benzodiazepines, narcotics) • Inability to perform spirometry • Refusal to provide informed consent Sample Size The sample size was calculated based on an assumed OSA prevalence of 88%, derived from prior literature (Lancaster et al.). Using a 95% confidence level and 10% absolute error, the estimated sample size was 64 patients, calculated using the formula: A total enumeration technique was used to include all eligible patients during the study period. Statistical Analysis Data were analyzed using SPSS version 20.0. Descriptive statistics were used for demographic and clinical data. Associations were tested using the Chi-square test for categorical variables and independent t-tests or ANOVA for continuous variables. A p-value < 0.05 was considered statistically significant. Data Collection Tools and Study Variables Data collection was conducted using a pre-designed, pre-tested semi-structured schedule that captured detailed patient history, including symptom duration, comorbidities, medication use, and smoking history. The schedule was administered by trained personnel under supervision. Additionally, relevant clinical information was obtained from outpatient department (OPD) records, admission files, and inpatient case sheets, which included HRCT imaging reports, spirometry results, and arterial blood gas analyses. All patients underwent a thorough clinical examination, focusing on anthropometric parameters and respiratory findings. Spirometry was performed using the GANSHORN PowerCube Diffusion+ system integrated with SCHILLER LFX software, to measure forced vital capacity (FVC) and assess lung function. For sleep study, Type 3 portable polysomnography (PSG) was conducted using the SomnotouchResp machine, which recorded the Apnoea-Hypopnea Index (AHI), minimum oxygen saturation (SpO₂), desaturation index, and apnoea duration. The PSG was conducted overnight under supervised conditions, and a minimum of 4 hours of total sleep time was required for data to be considered valid. The key variables studied included: • Demographic characteristics: age and sex • Clinical parameters: presence of cough and dyspnoea (either or both), comorbid conditions (including hypertension, diabetes mellitus, ischemic heart disease, GERD, and CKD), and smoking history (quantified using smoking index) • Anthropometric measurements: weight (kg), height (cm), body mass index (BMI in kg/m²), and neck circumference (cm) • Pulmonary function tests: particularly FVC, expressed as a percentage of the predicted value • Blood gas analysis: arterial partial pressure of oxygen (PaO₂) • Polysomnographic parameters: AHI (categorized as mild, moderate, or severe), minimum SpO₂, desaturation index, and maximum apnoea duration All data were recorded in a standardized format to ensure consistency and facilitate statistical analysis.

1. Baseline Demographic and Clinical Characteristics The study included a total of 64 patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF). The mean age of participants was 71.91 ± 5.78 years, with the majority falling into the older age categories. Specifically, 54.7% of patients were aged 65–74 years, while 32.8% were ≥75 years, and 12.5% were between 55–64 years. A substantial male predominance was observed, with 87.5% males and 12.5% females. In terms of smoking exposure, a moderate smoking index was most common, seen in 71.9% of participants, followed by mild (18.8%) and severe exposure (9.4%). The most frequently reported presenting symptom was a dry cough (43.75%), followed by dyspnoea (29.6%), while 26.5% experienced both. Among comorbid conditions, hypertension was most prevalent (59.4%), followed by diabetes mellitus (34.4%), ischemic heart disease (IHD) (14.1%), GERD (7.8%), and chronic kidney disease (CKD) (4.6%). Table 1. Baseline Demographic and Clinical Characteristics of the Study Population Variable Category Frequency (%) Age Group (years) 55–64 12.5 65–74 54.7 ≥75 32.8 Sex Male 87.5 Female 12.5 Smoking Index Mild 18.8 Moderate 71.9 Severe 9.4 Presenting Symptoms Dry cough 43.75 Dyspnoea 29.6 Both cough and dyspnoea 26.5 Comorbidities Hypertension 59.4 Diabetes Mellitus 34.4 Ischemic Heart Disease (IHD) 14.1 GERD 7.8 Chronic Kidney Disease (CKD) 4.6 2. Prevalence and Severity of Obstructive Sleep Apnoea (OSA) Among the 64 patients with Idiopathic Pulmonary Fibrosis (IPF), OSA symptoms were reported by 71.9%, while OSA was confirmed via polysomnography in 70.3% of patients. Severity classification based on the Apnoea-Hypopnea Index (AHI) revealed that moderate OSA was the most common (35.9%), followed by severe OSA (29.7%) and mild OSA (12.5%). These findings indicate a high burden of clinically significant OSA among patients with IPF, supporting the need for routine screening and early intervention. Table 2. Prevalence and Severity of OSA among IPF Patients OSA Category Frequency (%) Symptomatic for OSA 71.9 Confirmed OSA (AHI ≥ 5) 70.3 Severity - Mild (AHI 5–14) 12.5 - Moderate (AHI 15–29) 35.9 - Severe (AHI ≥ 30) 29.7 3. Association of OSA with Clinical Parameters Patients with OSA demonstrated significantly lower pulmonary function and arterial oxygenation compared to those without OSA. The mean forced vital capacity (FVC), expressed as a percentage of predicted value, was 58.7% in the OSA group compared to 68.3% in the non-OSA group (p = 0.001). Similarly, the mean arterial partial pressure of oxygen (PaO₂) was significantly lower in the OSA group (70.08 mmHg) than in those without OSA (81.63 mmHg, p = 0.001), indicating a more pronounced hypoxemic burden among IPF patients with OSA (Table 3). Table 3. Comparison of Clinical and Functional Parameters between OSA and Non-OSA Groups Parameter OSA Group (Mean) Non-OSA Group (Mean) p-value FVC (% predicted) 58.7 68.3 0.001 PaO₂ (mmHg) 70.08 81.63 0.001 4. Polysomnographic Features in OSA-Positive IPF Patients Among patients with confirmed OSA, polysomnographic analysis revealed notable sleep-disordered breathing abnormalities. The mean Apnoea-Hypopnea Index (AHI) was 28.91 ± 9.21 events/hour, indicating a predominance of moderate to severe OSA. The mean maximum apnoea duration recorded was 26.69 ± 10.87 seconds, reflecting significant nocturnal airway obstruction. Additionally, the mean desaturation index (events/hour) was 25.34 ± 12.89, and the mean minimum oxygen saturation (SpO₂) during sleep was 77.61 ± 7.25%, suggesting frequent and profound hypoxemic events during sleep (Table 4). These findings support the presence of clinically significant nocturnal hypoxemia in this patient cohort. Table 4. Polysomnographic Features in OSA-Positive IPF Patients Parameter Mean ± SD AHI (events/hour) 28.91 ± 9.21 Maximum Apnoea Duration (sec) 26.69 ± 10.87 Desaturation Index (/hour) 25.34 ± 12.89 Minimum SpO₂ (%) 77.61 ± 7.25 5. Anthropometric Correlates of OSA Severity A significant association was observed between anthropometric measurements and the severity of OSA, as stratified by the Apnoea-Hypopnea Index (AHI). Patients with severe OSA had higher body mass index (BMI) and neck circumference compared to those with mild or moderate AHI levels. Specifically, the mean BMI increased from 23.5 kg/m² in mild OSA to 27.8 kg/m² in severe cases (p = 0.031). Neck circumference showed a similar trend, ranging from 36.2 cm to 39.4 cm (p = 0.029). The prevalence of hypertension also rose significantly with increasing OSA severity, from 25.0% in the mild group to 78.9% in the severe group (p = 0.008), indicating a possible link between cardiovascular comorbidity and OSA burden in IPF (Table 5, Figure 4). Table 5. Anthropometric and Clinical Correlates Across AHI Severity Levels Parameter Mild AHI Moderate AHI Severe AHI p-value BMI (kg/m²) 23.5 25.6 27.8 0.031 Neck Circumference (cm) 36.2 37.8 39.4 0.029 Hypertension Prevalence (%) 25.0 54.6 78.9 0.008 6. Statistical Summary of Significant Associations Several statistically significant associations were identified between clinical variables and the presence or severity of obstructive sleep apnoea (OSA) in patients with idiopathic pulmonary fibrosis (IPF). These associations reinforce the interplay between pulmonary function, anthropometry, and cardiovascular comorbidity in the context of sleep-disordered breathing. Key associations include: • Lower PaO₂ levels in OSA patients compared to non-OSA counterparts (p = 0.001) • Reduced FVC (% predicted) in OSA patients (p = 0.001) • Progressive increase in BMI and neck circumference with escalating AHI severity (p = 0.031 and p = 0.029, respectively) • Significantly higher hypertension prevalence in patients with severe OSA (p = 0.008) Table 6. Summary of Statistically Significant Associations with OSA and Its Severity Variable Comparison p-value FVC (% predicted) OSA vs. Non-OSA 0.001 PaO₂ (mmHg) OSA vs. Non-OSA 0.001 BMI (kg/m²) Mild vs. Moderate vs. Severe AHI 0.031 Neck Circumference (cm) Mild vs. Moderate vs. Severe AHI 0.029 Hypertension Prevalence (%) Mild vs. Moderate vs. Severe AHI 0.008

In this prospective observational study, the prevalence of obstructive sleep apnoea (OSA) among patients with idiopathic pulmonary fibrosis (IPF) was found to be 70.3%, with moderate and severe OSA accounting for 35.9% and 29.7%, respectively. These results are consistent with previously reported figures, suggesting that OSA is highly prevalent in IPF populations. Mermigkis et al. reported a similar OSA prevalence of 66% among Greek patients with IPF using overnight polysomnography [7]. In a later publication, the same group emphasized that fibrotic lung changes may reduce lung volume and increase upper airway collapsibility, thereby facilitating OSA [8]. Rasche and Orth also observed that restrictive ventilatory mechanics in IPF could exacerbate nocturnal oxygen desaturation, promoting OSA development [9]. Our finding that patients with OSA had significantly lower forced vital capacity (FVC) than those without (58.7% vs. 68.3%, p = 0.001) supports this hypothesis. In addition, the arterial oxygen tension (PaO₂) was significantly lower in the OSA group (70.08 mmHg) compared to the non-OSA group (81.63 mmHg, p = 0.001), aligning with the Sleep Heart Health Study, which demonstrated that intermittent nocturnal hypoxemia correlates with increased cardiovascular risk [10]. The association between reduced pulmonary function and OSA was further validated by Lee et al., who reported that IPF patients with OSA had lower mean FVC values (59.2%) compared to those without OSA (70.5%) [11]. Kamgo et al., in a North Indian ILD population, similarly documented increased OSA prevalence among patients with lower lung function [12]. In our study, anthropometric factors such as body mass index (BMI) and neck circumference were also associated with AHI severity. Patients with severe OSA had a mean BMI of 27.8 kg/m² and neck circumference of 39.4 cm, compared to 23.5 kg/m² and 36.2 cm in mild OSA. Although obesity is less common in IPF than in the general OSA population, this trend aligns with previous findings and supports its role as a modifying factor [12]. Polysomnographic data in our study revealed a mean Apnoea-Hypopnea Index (AHI) of 28.91 ± 9.21 events/hour, maximum apnoea duration of 26.69 ± 10.87 seconds, and minimum SpO₂ of 77.61 ± 7.25%. These values are consistent with those reported by Mermigkis et al. [7], reinforcing the idea that IPF patients with OSA experience clinically significant sleep-disordered breathing. Khor et al. highlighted that ILD patients with OSA experience lower nocturnal oxygenation and higher mortality, supporting the clinical importance of our findings [19]. In contrast, the global population prevalence of OSA is substantially lower. Senaratna et al. estimated OSA prevalence at 22% in men and 17% in women in the general population [15], indicating that the burden in IPF patients is disproportionately high. This discrepancy may be due to disease-specific pathophysiological mechanisms, as well as diagnostic modality differences (e.g., Type III vs. full polysomnography), as noted in other studies [12,16]. Hypertension, observed in 59.4% of the overall cohort and 78.9% of those with severe OSA, was significantly associated with OSA burden (p = 0.008). Shahar et al. had previously shown that OSA is an independent risk factor for hypertension and cardiovascular disease in sleep-disordered populations [10]. Papadogiannis et al. further found that IPF patients with OSA had worse baseline function and outcomes but could benefit from positive airway pressure (PAP) therapy [17]. Obesity-related mechanical effects also play a role in respiratory compromise. Poulain et al. demonstrated that increased adiposity negatively affects thoracic compliance and gas exchange, contributing to respiratory burden in chronic lung diseases [18]. Khor et al. reinforced that OSA in ILD is not a benign comorbidity, but rather a pathophysiological amplifier that may accelerate disease progression [19]. Taken together, our findings underscore that OSA is not only highly prevalent but also clinically impactful in IPF patients. The consistent associations with reduced lung function, nocturnal desaturation, and systemic hypertension argue for routine OSA screening in all IPF patients, especially those with obesity or cardiovascular comorbidities. While diagnostic tools such as full PSG are ideal, even portable studies can offer valuable insights in resource-limited settings. Longitudinal studies are needed to determine whether early detection and treatment of OSA can alter the clinical trajectory of IPF. Limitations This study has several limitations. First, its single-centre, cross-sectional design restricts causal inference and generalizability. Second, the modest sample size highlights the need for larger, multi-centre studies. Third, sleep data were obtained using Type III polysomnography, which does not assess sleep stages or actual sleep duration, potentially underestimating OSA severity. Additionally, some patients had difficulty achieving adequate sleep duration in the hospital setting. Lastly, exclusion of patients with neurological, psychiatric, or other chronic pulmonary diseases may have limited sample diversity and real-world applicability.

Obstructive sleep apnoea (OSA) was highly prevalent among patients with idiopathic pulmonary fibrosis (IPF) in this cohort. Its presence was associated with reduced pulmonary function, lower oxygenation, and a higher burden of hypertension. Anthropometric measures such as increased BMI and neck circumference correlated with OSA severity. These findings support routine screening for OSA in IPF patients, particularly those with comorbid risk factors. Early identification may aid in risk stratification and integrated management to improve patient outcomes.

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