Study cohort
A total of 2,115 patients with IP from Beijing Chao-Yang Hospital were sequentially included from January 2017 to September 2019 prospectively. IP was diagnosed according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) Consensus Classification of IIPs [23]. All patients with IP underwent clinical examinations, laboratory tests, chest high-resolution computed tomography (HRCT), pulmonary function tests, and if necessary, pathological examinations at their first clinical visits [23].
Among enrolled patients, 30 patients were diagnosed with PM, 20 with DM, 33 with ADM and 41 with IPAF, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for IIM [24] and the ERS/ATS research statement of IPAF [5]. Of the 2,115 patients with IP, 42 underwent pathological examinations of lungs.
Data collection and definitions
At the first clinical visit, the patient medical records were reviewed to uniformly extract clinical data including demographics (age, sex, and smoking status), patient-reported information (date of symptom onset), clinical manifestations, physical examinations and comorbidities.
Serological markers were obtained within one month of presentation to the clinic including C-reactive protein, erythrocyte sedimentation rate, fibrinogen, immunoglobulin (Ig) A, IgG and IgM. Levels of autoantibodies, creatine kinase and cardiac troponin I were also recorded. MSA, including anti-ARS (anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ), anti-Mi-2, anti-MDA5, anti-TIF1γ, anti-NXP2, and anti-SAE were detected by immunoprecipitation as previously reported [25–27].
All enrolled patients underwent chest HRCT with a 1-s scan time, 0.625-mm sections, and 10-mm intervals from the lung apex to the base including both lungs in the field of view. Each HRCT scan was reviewed independently by two experienced thoracic radiologists blinded to the clinical data. HRCT patterns were assessed according to the classification of IIPs for the presence of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), organic pneumonia, or acute interstitial pneumonia (AIP) patterns [23]. The interobserver correlation was good. The kappa value was 0.83.
Pulmonary function test was performed for each patient. The test items included forced vital capacity (FVC), and the diffusing capacity of the lung for carbon monoxide (DLCO) using the single-breath method [28].
The smoking status was categorized into non-smokers, ex-smokers (quit smoking ≥ 12 months previously) and current smokers (currently smoking or quit smoking < 12 months previously). Acute (or subacute) onset was defined as less than three months from symptoms onset to the first clinical visit, and chronic onset was defined as more than three months. Malignancy was recorded if it occurred within three years before or after a positive detection of MSA [29]. Pulmonary hypertension was considered if the tricuspid regurgitation velocity ≤ 2.8 m/s and/or the systolic pulmonary arterial pressure ≥ 37 mmHg in echocardiography [30].
Follow-up and endpoint of the study
The outcome of this study was the progression of IP defined as a relative decrease of FVC% predicted ≥ 10%, a relative decrease of DLCO% predicted ≥ 15%, or death within 6 months of diagnosis [31]. The follow-up interval was 3 or 6 months and the follow-up period ended in September 2019. Survival time was calculated from the onset of symptoms to the outcome or end of the follow-up period.
Statistical analysis
Quantitative data were reported as means ± standard deviations or medians (interquartile ranges), and qualitative data were reported as numbers and percentages. Variables involved in cluster analysis included a binary had or did not have pulmonary symptoms (including cough, dyspnea), a binary had or did not have skeletal muscle symptoms (including proximal muscle weakness, dysphagia), a binary had or did not have UIP pattern, and the subtypes of MSA (anti-ARS or subtypes of anti-non-ARS MSA). These variables were available for all participants. Analysis of variance was used for comparisons of normally distributed quantitative data, the non-parametric Mann–Whitney U test was used to compare quantitative data with a non-normal distribution, and the chi-square test was used for comparisons of qualitative data. Multivariable Logistic regression was applied in determining potential risk factors for acute onset. Survival curves were obtained using Kaplan–Meier curves and compared with log-rank tests. The multivariable Cox proportional hazards model was constructed to identify prognostic factors. Statistical analysis was performed using SPSS software (version 23.0, IBM), and P < 0.05 was statistically significant.