Clinical Updates in Interstitial Lung Disease

Educational Objectives

The goal of this program is to improve management of interstitial lung disease (ILD). After hearing and assimilating this program, the clinician will be better able to:

1. Implement updated guidelines regarding the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF).
2. Appraise various treatment modalities for patients with IPF.

Summary

Interstitial lung disease (ILD): a heterogeneous group of disorders that cause inflammation and scarring of the lung parenchyma, pleura, or airways; Farrand et al (2023) classified ILD based on disease origin; >200 ILDs exist; of patients with ILD, epidemiologic studies show that ≈20% will have exposure-related ILD, ≈20% will have connective tissue ILD, ≈20% will have idiopathic pulmonary fibrosis (IPF), and ≈40% will have ILD that is idiopathic, unclassifiable, or secondary to other causes

Clinical practice guideline updates (Raghu et al [2022]): diagnosis — the classic radiographic pattern of usual interstitial pneumonia (UIP) includes reticulation, traction bronchiectasis, and honeycombing; reticulation and traction bronchiectasis, but not honeycombing, are present in probable UIP; the presence of a probable UIP pattern can support the diagnosis of IPF; though suspicion for IPF is higher in older patients and when there is traction bronchiectasis and extensive reticulation, additional testing is still recommended for younger patients with early, mild disease (per Brownell et al [2017], patient age and gender, plus total traction bronchiectasis score significantly improve the positive predictive value of a possible UIP pattern for diagnosing IPF); other diagnostic modalities — cryobiopsy is an acceptable alternative to surgical lung biopsy; use of genomic classifiers is neither supported nor refuted because of insufficient data regarding false-negative results; treatment — no role exists for empiric antacid therapy or antireflux surgery to improve respiratory outcomes; progressive pulmonary fibrosis (PPF) — defined as non-IPF ILD with at least 2 of 3 criteria (ie, worsening respiratory symptoms, physiologic evidence of progression, radiologic evidence of disease progression) occurring within the past year; insufficient data exist to support the use of pirfenidone (PFD); the INBUILD trial (Kolb et al [2023]) demonstrated a slowed rate of decline of lung function among patients with PPF prescribed NTD (recommended for treatment of PPF); treatment of IPF — includes pharmacologic (eg, antifibrotic therapy), supplemental oxygen therapy, and pulmonary rehabilitation (PR); assess for comorbid, eg, sleep apnea, pulmonary hypertension, lung cancer; consider early referral for lung transplantation (LT; currently the only cure for IPF); perform pulmonary function testing and walking testing every 6 mo; consider imaging for changes in symptoms, concern for lung cancer, and acute exacerbation; consider pulmonary embolism as a differential diagnosis for patients with acute worsening of symptoms; use of corticosteroids is recommended for acute exacerbation of IPF (rare), though data are mixed; consider LT and palliative care for respiratory failure

Treatment of scleroderma-associated ILD (SSc-ILD; Raghu et al [2024]): nintedanib — Campochiaro et al (2023) found that NTD slowed the rate of decline in lung function in patients with mild to moderate SSc-ILD; ≈76% of patients taking NTD experienced diarrhea as an adverse event (AE); tocilizumab — Khanna et al (2021) showed that tocilizumab stabilized lung function in patients with mild to moderate SSc-ILD; the most common AE was infection; recommendations — mycophenolate mofetil (MMF) is strongly recommended as first-line therapy for SSc-ILD; therapies with conditional recommendations include cyclophosphamide, rituximab, tocilizumab, NTD, and NTD + MMF; insufficient data exist regarding MMF in combination with other drug therapies; tocilizumab may be appropriate for someone with high inflammatory markers; NTD can be an option for patients who present with UIP-pattern SSc-ILD, although tolerability may be a concern with NTD + MMF (may be an option for patient with less dysmotility); more research is needed for PFD; avoid high-dose corticosteroids, which can cause scleroderma renal crisis

Palliative care (PC) in serious respiratory illness (Sullivan et al [2022]): types — primary palliative care (PPC) can be provided by any clinician; secondary and tertiary PC (for patients approaching end of life) require PC experts; components of PPC — includes symptom assessment and management, advance care planning (ACP), goals of care, care coordination, referral to secondary PC in a timely way, and transition to hospice; PC reminds clinicians to focus on quality of life and whole-person care rather than lung function alone; timeline — consider PPC for patients with severely compromised lung function, need for oxygen, decline in walking distance, and consideration for LT; assess symptom management and caregiver support; consider secondary PC for patients with severely advanced disease, pulmonary cachexia, and <30% ratio of forced vital capacity (FVC) to forced expiratory volume in 1 sec; advance care planning — can be incorporated into all patient visits; encourage patients to consider ACP early to aid with hospital admission or end-of-life care; state-based websites allow patients to create their own plans

Recent evidence: West et al (2023) — showed that 100 mg of nebulized PFD given twice daily provides improved stability of FVC vs 50 mg in patients with mild to moderate IPF not already taking an oral medication; PFD is generally well-tolerated but causes, eg, cough, mild rash, nausea, fatigue; FIBRONEER-IPF trial (Richeldi et al [2022]) — found that an oral phosphodiesterase 4B inhibitor (BI 1015550) stabilizes lung function over 12 wk in patients with IPF, compared with placebo; diarrhea is the most common AE; PACIFY COUGH trial (Wu et al [2024]) — demonstrated that 5 mg controlled-release morphine given twice daily to patients with early IPF and refractory cough reduces cough frequency by ≈40%, compared with placebo; serious AEs include gastrointestinal (GI) effects, hypersomnia (≈9%), and lethargy (≈5%); FITNESS trial (Kataoka et al [2023]) — found that, compared with placebo, patients with IPF prescribed 12 wk intensive PR + 40 wk home maintenance experienced prolonged improved endurance time (associated with improved quality of life), though similar 6-min walking distance; PR can be difficult to maintain (only ≈50% of individuals continued home maintenance) and also difficult to access (virtual PR may be suitable for patients who live in rural areas); MADIET trial (Molina-Molina et al [2023]) — noted a significantly decreased incidence of PFD-related GI AEs among individuals with IPF who consumed a diet rich in monounsaturated fatty acids, rather than a diet high in saturated fatty acids, with no impacts on PFD absorption or efficacy

Readings

Campochiaro C, De Luca G, Lazzaroni MG, et al. Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study. RMD Open. 2023;9(1):e002850. doi:10.1136/rmdopen-2022-002850; Farrand E, Collard HR, Guarnieri M, et al. Extracting patient-level data from the electronic health record: expanding opportunities for health system research. PLoS One. 2023;18(3):e0280342. doi:10.1371/journal.pone.0280342; Kataoka K, Nishiyama O, Ogura T, et al. Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial. Thorax. 2023;78(8):784-791. doi:10.1136/thorax-2022-219792; Khanna D, Lin CJF, Furst DE, et al. Long-term safety and efficacy of tocilizumab in early systemic sclerosis-interstitial lung disease: open-label extension of a phase 3 randomized controlled trial. Am J Respir Crit Care Med. 2022;205(6):674-684. doi:10.1164/rccm.202103-0714OC; Molina-Molina M, Shull JG, Vicens-Zygmunt V, et al. Gastrointestinal pirfenidone adverse events in idiopathic pulmonary fibrosis depending on diet: the MADIET clinical trial. Eur Respir J. 2023;62(4):2300262. doi:10.1183/13993003.00262-2023; Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022;205(9):e18-e47. doi:10.1164/rccm.202202-0399ST; Raghu G, Montesi SB, Silver RM, et al. Treatment of systemic sclerosis-associated interstitial lung disease: evidence-based recommendations. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2024;209(2):137-152. doi:10.1164/rccm.202306-1113ST; Rahaghi FF, Hsu VM, Kaner RJ, et al. Expert consensus on the management of systemic sclerosis-associated interstitial lung disease. Respir Res. 2023;24(1):6. doi:10.1186/s12931-022-02292-3; Richeldi L, Azuma A, Cottin V, et al. Trial of a preferential phosphodiesterase 4B inhibitor for idiopathic pulmonary fibrosis. N Engl J Med. 2022;386(23):2178-2187. doi:10.1056/NEJMoa2201737; Sullivan DR, Iyer AS, Enguidanos S, et al. Palliative care early in the care continuum among patients with serious respiratory illness: An official ATS/AAHPM/HPNA/SWHPN policy statement. Am J Respir Crit Care Med. 2022;206(6):e44-e69. doi: 10.1164/rccm.202207-1262ST; West A, Chaudhuri N, Barczyk A, et al. Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial. Thorax. 2023;78(9):882-889. doi:10.1136/thorax-2022-219391; Wu Z, Spencer LG, Banya W, et al. Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial. Lancet Respir Med. doi:10.1016/S2213-2600(23)00432-0.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Shah was recorded at Interstitial Lung Disease: The Changing Landscape, held on January 27, 2024, in San Francisco, CA, and presented by the University of California, San Francisco School of Medicine. For information about upcoming CME activities from this presenter, please check https://meded.ucsf.edu/cme. Audio Digest thanks the speakers and the University of California, San Francisco School of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

IM712101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.