Comorbidities’ Effect on IPF: Pathogenesis and Management
Abstract
:1. Introduction
2. Methodological Approach
Pathogenesis of IPF
3. Identified Comorbidities and Their Management
3.1. Respiratory Comorbidities
Pulmonary Emphysema (Combined Pulmonary Fibrosis and Emphysema)
3.2. Cardiovascular Disorders
3.2.1. Pulmonary Hypertension
3.2.2. Ischemic Heart Disease
3.2.3. Arrhythmias
3.3. Gastrointestinal Comorbidities
Gastroesophageal Reflux Disease
3.4. Sleep-Related Breathing Disorders
Obstructive Sleep Apnea
3.5. Oncological Comorbidities
Lung Cancer
3.6. Neuropsychiatric Comorbidities
Anxiety and Depression
3.7. Acute Exacerbations of IPF
4. Conclusions and Future Perspectives
5. Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Comorbidity | Prevalence in IPF | Impact on IPF | Key Tests | Management Strategies | Impact on Antifibrotic Therapy |
---|---|---|---|---|---|
Pulmonary emphysema and/or COPD | 6–67% [35,36]. | Mortality > emphysema alone [38]. Additional negative effect on outcomes [37,38,40]. Association with LC and PH in 15–30% of CPFE [35,41,42,43]. | PFT DLCO [39], HRCT [37]. | Antifibrotics + bronchodilators + smoking cessation + O2 supplementation for desaturation + pulmonary rehabilitation + vaccines [6,36,37,38,39,46]. | Both antifibrotic drugs have a similar effect on CPFE as on IPF alone [44,45]. |
Pulmonary hypertension | from 8–15% at diagnosis, up to 86% at lung transplantation [52]. | Increased disease burden and poor prognosis [47,48,49,50,51]. | TTE estimating RVSP [67], echocardiographic score for severe PH [72]. RHC gold standard [68,73]. | O2 therapy for hypoxia + antifibrotics + referral for lung transplantation + pulmonary rehabilitation [68,74]. Some evidence for treprostinil [74,77,78,79,80], iNO [81,82,83], and sildenafil [86]. | |
Ischemic heart disease | Up to 68% [95]. | Second leading cause of death (~10%) [92,93,94,95,96,97]. Worse outcomes when significant CAD. | HRCT scans assessing CAC score as a screening tool [117]. | ||
Arrhythmias | 6–19% [30]. | Biomarkers like CRP and BNP may predict AF risk [118]. decreased FEV1% and FVC% independent risk factors for AF in IPF and COPD [120]. IPF risk factor for arrhythmias after lung transplantation [119,121,122]. | |||
Gastro-esophageal reflux disease | 60–80%, [123,124,125,126]. | Often silently [123,124,125,126]. | Esophageal pH monitoring: gold standard for diagnosis [127,128]. | antacid therapy only when symptomatic GERD [6,39,124,131,142]. Anti-reflux surgery not routinely recommended [141]. | common side effect of pirfenidone [143]. |
Obstructive sleep apnea | 59–88% [144,145] | Abnormal sleep macro- and microarchitecture impacting QoL [146] with worse survival | Crucial early detection of SRBD via nocturnal respiratory polygraphy [146]. | O2 therapy for REM-related SBD and CPAP for OSA [145,146]. | nintedanib improves anxiety/depression and thus potentially sleep quality [78]. Insomnia: side effect of pirfenidone (~10%) [44,153]. |
Lung cancer | 3–22% [155,156,157,158,159]. Higher risk in CPFE (up to 12%) and in ILAs [38]. | Poor survival, often driven by the malignancy [164,170,171]. SCC prevalence > AC, frequently arising in peripheral, fibrotic areas, particularly honeycomb regions [154,168,169,170,171]. | Annual HRCT for early LC detection [160]. | Surgical resection and radiation therapy limited by extensive fibrosis and risk of post-operative complications [170,173,174]. Tissue-sparing surgery, careful fluid management, and low-tidal-volume ventilation [171,174]. Carboplatin-based regimens are relatively safer than many antineoplastic agents [180]. Combination therapy under investigation [193]. | Perioperative pirfenidone may reduce post-operative exacerbation risk [175] Pirfenidone inhibits epithelial–mesenchymal transition and promotes apoptosis in cancer-associated fibroblasts [163,165,170,181,182]. Nintedanib antitumor effects in preclinical models [194,195] and in case reports on NSCLC [202,203,204]. Lower LC incidence and LC-related mortality in observational studies on antifibrotic therapy [184,185,190,191]. |
Anxiety and depression | Anxiety 30–60% Depression 20–50% >General population and other chronic respiratory diseases [24,30] | Worse quality of life, symptom burden, and overall prognosis [24,206]. Negatively affect treatment adherence, engagement in self-management behaviors, and overall coping abilities [206]. | Screening for psychiatric comorbidities should be a routine part of IPF care [207] | Holistic approach: pulmonary rehabilitation, CBT, mindfulness-based stress reduction, and patient support groups [207]. Antidepressants or anxiolytics [207]. Early palliative care interventions, improving QoL [21,22]. |
Drug Class | Pirfenidone | Nintedanib |
---|---|---|
Bronchodilators | No clinically relevant interactions known. | No clinically relevant interactions known. |
Inhaled corticosteroids | No significant interaction; no specific management. | No significant interaction; no specific management. |
Antiplatelets (e.g., ASA and clopidogrel) [246] | Use with caution: potential increased bleeding risk not documented but theoretically possible. | Increased bleeding risk. Use with caution, especially with ASA or clopidogrel. |
Anticoagulants (e.g., warfarin and DOACs) [246,247] | Use with caution. No direct interaction is known, but bleeding risk should be considered. | Increased bleeding risk. Caution advised when co-administered with oral anticoagulants. |
Beta-blockers | No significant interaction; no specific management. | No significant interaction; no specific management. |
Antiarrhythmics | No significant interaction reported; monitor QT interval if applicable. | No significant interaction reported; monitor QT interval if applicable. |
Antacids/PPIs (e.g., omeprazole) | Possible reduced absorption in the presence of elevated gastric pH. Administer separately [248]. | No clinically significant interaction observed [249]. |
Drugs for pulmonary hypertension | No direct interaction with sildenafil [85] or other vasodilators, but additive vasodilatory effects are possible; monitor blood pressure. | No direct interaction is known, but monitor hemodynamic tolerance. |
Antidepressants (e.g., SSRIs, SNRIs, and TCAs) | No significant documented interaction. | No clinically significant interaction documented. |
Anxiolytics (e.g., benzodiazepines) | No known significant interaction. | No known significant interaction. |
Statins | Potential for hepatotoxicity; monitor liver function. | Possible additive hepatotoxicity; monitor liver enzymes |
Drugs for lung cancer | Possible interactions with CYP1A2 inhibitors (e.g., some chemotherapeutics). Use caution. (A) | Potential interactions with CYP3A4 (osimertinib) and P-gp substrates. Monitor closely. (B) |
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Salotti, A.; Chianese, M.; Romallo, A.; De Nes, A.; Angoni, D.; Galantino, A.; Chernovsky, M.; Mondini, L.; Salton, F.; Confalonieri, P.; et al. Comorbidities’ Effect on IPF: Pathogenesis and Management. Biomedicines 2025, 13, 1362. https://doi.org/10.3390/biomedicines13061362
Salotti A, Chianese M, Romallo A, De Nes A, Angoni D, Galantino A, Chernovsky M, Mondini L, Salton F, Confalonieri P, et al. Comorbidities’ Effect on IPF: Pathogenesis and Management. Biomedicines. 2025; 13(6):1362. https://doi.org/10.3390/biomedicines13061362
Chicago/Turabian StyleSalotti, Andrea, Maria Chianese, Antonio Romallo, Anna De Nes, Darina Angoni, Alessandra Galantino, Maria Chernovsky, Lucrezia Mondini, Francesco Salton, Paola Confalonieri, and et al. 2025. "Comorbidities’ Effect on IPF: Pathogenesis and Management" Biomedicines 13, no. 6: 1362. https://doi.org/10.3390/biomedicines13061362
APA StyleSalotti, A., Chianese, M., Romallo, A., De Nes, A., Angoni, D., Galantino, A., Chernovsky, M., Mondini, L., Salton, F., Confalonieri, P., Cifaldi, R., Geri, P., Pividori, M., Bandini, G., Hughes, M., Confalonieri, M., Maggisano, M., & Ruaro, B. (2025). Comorbidities’ Effect on IPF: Pathogenesis and Management. Biomedicines, 13(6), 1362. https://doi.org/10.3390/biomedicines13061362