Matucci‐Cerinic, Marco

Background Gastro-oesophageal reflux disease (GORD) occurs in most (∼75%) patients with systemic sclerosis (SSc) and significantly impacts quality of life. Current recommendations lack depth and therefore our aim was to produce practical, consensus-based recommendations for refractory SSc-related GORD. Methods An international, multidisciplinary steering board (SB) was assembled (n=19) consisting of clinicians (rheumatologists, gastroenterologists, gastrointestinal surgeons), an expert methodologist and patient representation. After reviewing the latest definitions of GORD and refractory GORD in the published literature, the SB collectively devised a practical definition of SSc refractory-GORD. Initial recommendations were drafted/agreed on by the SB based on review of the existing guidelines, published literature and expert opinion. Two online voting rounds were conducted to determine whether items should be accepted, with >75% and >60% SB agreement required for first and second rounds, respectively. Results There was a good response/completion rate for the initial (74%) and final (84%) voting rounds. The SB agreed on all 36 draft recommendations. The majority (n=34) were approved in the first round. Recommendations were organised according to the following categories: general approach to management (n=5), assessment (n=6), non-pharmacological (n=2) and pharmacological (n=10) management, endoscopic and surgical treatment (n=3), and special circumstances including refractory GORD and SSc-interstitial lung disease (n=3), myositis and SSc connective tissue disease-overlap (n=3) and perilung transplant (n=4). Conclusion The group of experts has drafted extended and practical recommendations for the management of SSc refractory-GORD. The necessity of a structured approach and a patient assessment is highlighted in order to provide a multidisciplinary approach to the tailored choice of the treatment. Our work also has also identified significant unmet needs and has provided a research agenda to advance the field.

Objective Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest risk of developing ILD and are therefore candidates for screening for this complication of the underlying disease. Methods A systematic literature review was performed using PubMed, Embase and Scopus over a 10-year period up to July 2021. Publications reporting patient-level factors in patients with RA with and without ILD that were assessed before development of ILD (or were unchanged over time and therefore could be extrapolated to before development of ILD) were retrieved for assessment of evidence. Genetic variation in MUC5B and treatment with methotrexate were not included in the assessment of evidence because these factors have already been widely investigated for association with ILD. Results We found consistent associations of age, sex, smoking status and autoantibodies with development of ILD. For biomarkers such as Krebs von den Lungen 6, which have been shown to be diagnostic for ILD, there were no publications meeting criteria for this study. Conclusions This analysis provides an initial step in the identification of patient-level factors for potential development of a risk algorithm to identify patients with RA who may be candidates for screening for ILD. The findings represent a useful basis for future research leading to an improved understanding of the disease course and improved care for patients with RA at risk of development and progression of ILD.

Bronchoalveolar lavage and lung biopsy (LBx) are helpful in patients with connective tissue diseases (CTD) and interstitial lung diseases (ILD) regardless of cause, including infectious, noninfectious, immunologic, or malignant. The decision whether to perform only bronchoalveolar lavage (BAL), and eventually a subsequent LBx in case of a nondiagnostic lavage, or one single bronchoscopy combining both sampling methods depends on the clinical suspicion, on patient’s characteristics (e.g. increased biopsy risk) and preferences, and on the resources and biopsy techniques available locally (e.g. regular forceps versus cryobiopsy). In CTD-ILD, BAL has major clinical utility in excluding infections and in the diagnosis of specific patterns of acute lung damage (e.g. alveolar hemorrhage, diffuse alveolar damage, and organizing pneumonia). LBx is indicated to exclude neoplasm or diagnose lymphoproliferative lung disorders that in CTD patients are more common than in the general population. Defining BAL cellularity and characterizing the CTD-ILD histopathologic pattern by LBx can be helpful in the differential diagnosis of cases without established CTD [e.g. ILD preceding full-blown CTD, interstitial pneumonia with autoimmune features (IPAF)], but the prognostic and theragnostic role of those findings remains unclear. Few studies in the pretranscriptomics era have investigated the diagnostic and prognostic role of BAL and LBx in CTD-ILD, and it is reasonable to hypothesize that future studies conducted applying innovative techniques on BAL and LBx might open new and unexpected avenues in pathogenesis, diagnosis, and treatment approach to CTD-ILD. This is particularly desirable now that a new drug treatment era is emerging, in which we have more than one therapeutic choice (immunosuppressive agents, antifibrotic drugs, and biological agents). We hope that future research will pave the path toward precision medicine providing data for a more accurate ILD-CTD endotyping that will guide the physicians through targeted therapeutic choices, rather than to the approximative approach ‘one drug fits them all’.

Abstract Rationale Lung biopsy (LBx) has a relevant role in the prediction of prognosis of interstitial lung diseases (ILDs), but its impact on the clinical management of patients remains unexplored. Objectives This study evaluates whether LBx may change the therapeutic strategy and assesses the effect of diagnostic reclassification after LBx on long-term prognosis. Methods We evaluated the LBx of 426 consecutive patients with ILDs, without a definite usual interstitial pneumonia pattern on high-resolution computed tomographic imaging. A total of 266 patients underwent transbronchial lung cryobiopsy (TBLC), and 160 patients underwent surgical lung biopsy (SLB). The multidisciplinary team (MDT) determined a diagnosis with high or low confidence, and a management strategy, both before and after the LBx data. Results Final MDT diagnoses were 189 idiopathic pulmonary fibrosis (IPF), 143 non-IPF fibrotic ILDs, and 94 nonfibrotic ILDs. LBx data changed the management strategy in 145 cases (34%), with similar results for TBLC and SLB (the treatment strategy changed in 31.5% of TBLC cases, 84/266, P < 0.001, and in 38% of SLB, 61/160, P < 0.001). After LBx, the MDT was less inclined to “wait and see” (from 15% to 4% of cases, P < 0.001) or to prescribe steroids only (from 54% to 37%, P < 0.001) and was more confident to treat with antifibrotics (from 23% to 44%, P < 0.001) or immunosuppressive drugs (from 7% to 14%, P < 0.001). The therapeutic strategy changed in 70% of reclassified cases (60/85) and in 59% of cases in which LBx increased the MDT confidence (84/142). Reclassification significantly impacted the outcome. The cases classified as non-IPF by clinician and radiologist and then reclassified to be IPF after LBx showed a significantly worse survival compared with non-IPF confirmed cases (adjusted hazard ratio [HR], 3.8; 95% confidence interval [CI], 1.75–8.3); P = 0.001. Cases initially classified as IPF and then reclassified as non-IPF after LBx showed a better prognosis compared with IPF confirmed cases (HR, 0.41; 95% CI, 0.18–0.94; P = 0.03). Conclusions Reclassification of cases with LBx data increased diagnostic confidence and changed the therapeutic strategy in one-third of cases. Pathologic reclassification of cases refined prognosis prediction. Patients classified as non-IPF by clinician and radiologist and then reclassified IPF after LBx had worse prognosis compared with the non-IPF confirmed cases.