Clinical features and outcomes of small airway disease in ANCA-associated vasculitis.

BACKGROUND AND OBJECTIVE: To clarify the prevalence, features and outcomes of small airway disease (SAD) in a Chinese cohort with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) related pulmonary involvement. METHODS: SAD was recorded when the manifestations of either centrilobular nodules or air trapping were observed according to CT scans, except for infection or other airway-related comorbidities. Baseline and follow-up data were collected retrospectively. RESULTS: Of the 359 newly diagnosed AAV patients with pulmonary involvement, 92 (25.6%) had SAD, including 79 (85.9%) cases of anti-MPO-ANCA positive, 9 (9.8%) cases of anti-PR3-ANCA positive and 2 (2.2%) cases of double positive. Patients with SAD were more likely to be younger, female, non-smokers, have more ear-nose-throat (ENT) involvement, and have higher baseline Birmingham Vasculitis Activity Score (BVAS) compared to patients without SAD. Several AAV-related SAD patients have improved lung function and CT scans after immunosuppressive therapy. Patients with SAD had a better prognosis compared to those without SAD. When dividing all patients into three groups: isolated SAD (only small airway involvements), SAD with other lower airway involvements, and non-SAD, patients in the SAD with other lower airway involvements group had the highest risk of infection, while patients in the non-SAD group had the worst long-term outcomes. Similar results were observed in anti-MPO-ANCA positive patients when performing subgroup analyses. CONCLUSION: SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features. It is vital to focus on SAD because of its association with prognosis and infection in AAV patients, especially in anti-MPO-ANCA positive patients. Moreover, SAD might represent a better response to immunosuppressors.

The long-term and short-term effects of ambient air pollutants on sleep characteristics in the Chinese population: big data analysis from real world by sleep records of consumer wearable devices.

Several studies on long-term air pollution exposure and sleep have reported inconsistent results. Large-scale studies on short-term air pollution exposures and sleep have not been conducted. We investigated the associations of long- and short-term exposure to ambient air pollutants with sleep in a Chinese population based on over 1 million nights of sleep data from consumer wearable devices. Air pollution data including particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) were collected from the Ministry of Ecology and Environment. Short-term exposure was defined as a moving average of the exposure level for different lag days from Lag0 to Lag0-6. A 365-day moving average of air pollution was regarded as long-term exposure. Sleep data were recorded using wearable devices from 2017 to 2019. The mixed-effects model was used to evaluate the associations. We observed that sleep parameters were associated with long-term exposure to all air pollutants. Higher levels of air pollutant concentrations were associated with longer total sleep and light sleep duration, shorter deep sleep duration, and decreases in wake after sleep onset (WASO), with stronger associations of exposures to NO2 and CO [a 1-interquartile range (IQR) increased NO2 (10.3 µg/m3) was associated with 8.7 min (95% CI: 8.08 to 9.32) longer sleep duration, a 1-IQR increased CO (0.3 mg/m3) was associated with 5.0 min (95% CI: - 5.13 to - 4.89) shorter deep sleep duration, 7.7 min (95% CI: 7.46 to 7.85) longer light sleep duration, and 0.5% (95% CI: - 0.5 to - 0.4%) lower proportion of WASO duration to total sleep]. The cumulative effect of short-term exposure on Lag0-6 is similar to long-term exposure but relatively less. Subgroup analyses indicated generally greater effects on individuals who were female, younger (< 45 years), slept longer (≥ 7 h), and during cold seasons, but the pattern of effects was mixed. We supplemented two additional types of stratified analyses to reduce repeated measures of outcomes and exposures while accounting for individual variation. The results were consistent with the overall results, proving the robustness of the overall results. In summary, both short- and long-term exposure to air pollution affect sleep, and the effects are comparable. Although people tend to have prolonged total sleep duration with increasing air pollutant concentrations, their sleep quality might remain poor because of the reduction in deep sleep.

Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community.

OBJECTIVE: This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. METHODS: Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40-75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. RESULTS: A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245-2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. CONCLUSION: These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.

Patterns of Interstitial Lung Disease and Prognosis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). OBJECTIVES: We aimed to clarify the clinical predictors of mortality in a cohort of patients with AAV-related ILD (AAV-ILD). METHOD: We retrospectively identified AAV-ILD patients seen at Peking University First Hospital from January 2010 to June 2020 and manually screened for study inclusion. Baseline computed tomography (CT) images were further classified as nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), and unclassified ILD. Disease characteristics and other pulmonary findings including pulmonary function test and bronchoalveolar lavage (BAL) were also evaluated. Multivariable Cox regression analysis was performed to identify clinical predictors of mortality. RESULTS: The cohort included 204 patients with AAV-ILD, 152 had UIP on CT (AAV-UIP), 39 had NSIP on CT (AAV-NSIP), 3 had OP, and 10 had unclassified ILD. Microscopic polyangiitis was more prevalent in patients with UIP, while granulomatosis with polyangiitis was more common in the NSIP and OP groups, and eosinophilic granulomatosis with polyangiitis was more frequent in patients with unclassified ILD. ILD diagnosis before AAV was more common in patients with either UIP or NSIP patterns. During the median follow-up of 40 months, 44 (21.6%) patients died. One- and 5-year overall survival rates were 88.2% (95% CI, 83.7-92.7%) and 81.0% (95% CI, 74.9-87.1%) for the entire cohort. Patients with UIP patterns had the worst prognosis, while those with NSIP patterns had the best long-term outcome. Specifically, patients with UIP patterns had an approximately 5-fold risk of death compared to those with NSIP. After controlling for potential confounding factors, we observed that each 10% increase in the BAL fluid neutrophil percentage was associated with nearly a 20% increased risk of death (HR 1.195, 95% CI 1.018-1.404). CONCLUSIONS: Clinical characteristics and survival differ between subgroups defined by CT patterns. BAL fluid neutrophilia is an independent predictor of mortality among AAV-ILD patients, and therefore, the clinical utility of BAL at the time of AAV diagnosis should be considered.

Risk Factors for Immune Checkpoint Inhibitor-Related Pneumonitis in Cancer Patients: A Systemic Review and Meta-Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to one of the common and quite serious immune-related adverse events (irAEs) in a real-world setting, namely, checkpoint inhibitor pneumonitis (CIP). OBJECTIVE: We aimed to investigate the potential risk factors for CIP in cancer patients treated by ICIs and quantify the association. METHODS: We conducted a systematic literature review in PubMed, EMBASE, and Web of Science from January 1, 2000, to March 20, 2022, with no study design restrictions. Studies evaluating the risk factors for CIP in cancer patients treated with ICIs-containing regimes were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for risk factors of CIP by using random-effect model. Heterogeneity was assessed by sensitivity analysis and subgroup analysis regarding CIP severity, geographical regions, cancer types, treatment regimes, and ICI types. RESULTS: A total of 35 studies comprising 142,703 patients were eventually included. The incidence of grade I-V and grade III-V CIP in cancer patients was 0.16 (95% CI: 0.14-0.18) and 0.06 (95% CI: 0.05-0.08), respectively. When combining the adjusted ORs, the following risk factors were significantly associated with the development of CIP: squamous cell carcinoma (OR: 1.31, 95% CI: 1.18-1.45), previous thoracic radiotherapy (OR: 2.07, 95% CI: 1.34-3.19), preexisting radiation-induced pneumonitis (OR: 3.62, 95% CI: 1.53-8.58), preexisting respiratory disease (OR: 2.43, 95% CI: 1.45-4.07), preexisting interstitial lung disease (OR: 5.78, 95% CI: 3.08-10.85), preexisting ground glass attenuation (OR: 11.48, 95% CI: 1.13-116.74), preexisting honeycombing (OR: 6.11, 95% CI: 2.37-15.79), preexisting pulmonary emphysema (OR: 2.72, 95% CI: 1.00-7.36), use of pembrolizumab (OR: 2.89, 95% CI: 1.56-5.35, I2 = 0%), high PD-L1 expression (OR: 3.59, 95% CI: 1.23-10.50), and hypoalbuminemia (OR: 0.3, 95% CI: 0.14-0.64). When including the crude ORs, smoking history (OR: 1.39, 95% CI: 1.14-1.71), neutrophil-lymphocyte ratio (OR: 1.04, 95% CI: 1.01-1.08), and c-reactive protein (OR: 1.08, 95% CI: 1.01-1.16) were also risk factors for CIP. CONCLUSION: Histological characteristics, specific previous lung diseases and treatment history, treatment regimen, PD-L1 expression level, and serological biomarkers are all closely associated with the development of CIP. These findings would be useful for oncologists to optimize the appropriate options of ICIs and close monitoring during immunotherapy treatments, particularly for patients identified as having a higher risk for CIP.

Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients.

OBJECTIVE: The aim of this study was to clarify the clinical characteristics and long-term outcomes of ANCA-associated vasculitis (AAV) patients with pulmonary involvement from a single Chinese cohort. METHODS: Newly diagnosed AAV patients with pulmonary involvement, as defined by CT, were recruited from January 2010 to June 2020. Clinical data and CT images were collected retrospectively. Baseline CTs were evaluated and re-classified into four categories: interstitial lung disease (ILD), airway involvement (AI), alveolar hemorrhage (AH), and pulmonary granuloma (PG). RESULTS: A total of 719 patients were newly diagnosed with AAV, 366 (50.9%) of whom combined with pulmonary involvement at baseline. Among the AAV cases with pulmonary involvement, 55.7% (204/366) had ILD, 16.7% (61/366) had AI alone, 14.8% (54/366) had PG, and 12.8% (47/366) had AH alone. During follow-up of a median duration of 42.0 months, 66/366 (18.0%) patients died, mainly died from infections. Survival, relapse, and infection were all significantly different based on the radiological features. Specifically, the ILD group tends to have a poor long-term prognosis, the PG group is prone to relapse, and the AI group is apt to infection. The AH group has a high risk of both early infection and relapse, thus a poor short-term prognosis. CONCLUSION: AAV patients with diverse radiological features have different clinical characteristics and outcomes. Therefore, the intensity of immunosuppressive therapy must be carefully valued by considering the baseline CT findings among AAV patients with pulmonary involvement.

Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis.

Several retrospectivee described the association of interstitial lung disease (ILD) and ANCA-associated vasculitis (AAV). However, the relationship between the ILD and mortality in AAV patients have not been established so far. This study aims to estimate the relevance of AAV-associated-ILD (AAV-ILD) and mortality risk by conducting a systematic review and meta-analysis.A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies. Summary estimates were derived with a random-effects model and reported as risk ratio (RR), tested for publication bias and heterogeneity. Ten retrospective cohort studies were included, comprising 526 AAV-ILD patients enrolled from 1974 to 2018. Meta-analysis yielded a pooled RR of 2.90 (95% confidence interval 1.77-4.74) for death among those with AAV-ILD compared to control group. UIP pattern was associated with an even poorer prognosis in comparison to non-UIP pattern (RR 4.36, 95% confidence interval 1.14-16.78). Sensitivity analysis suggested that the meta-RR result was not skewed by a single dominant study. ILD might be associated with a higher mortality risk in AAV patients.