Introduction: Small airway dysfunction (SAD) commonly presents in patients with classic asthma, which is associated with airway inflammation, disease severity, and asthma control. However, the prevalence of SAD, its relationship with cough severity and airway inflammation, and its development after antiasthmatic treatment in patients with cough variant asthma (CVA) need to be clarified. This study aimed to investigate the prevalence of SAD and its relationship with clinical and pathophysiological characteristics in patients with CVA and the change in small airway function after antiasthmatic treatment.Methods: We retrospectively analyzed 120 corticosteroid-naïve patients with CVA who had finished a standard questionnaire and relevant tests in a specialist cough clinic, such as cough visual analog scale (VAS), differential cells in induced sputum, fractional exhaled nitric oxide (FeNO) measurement, spirometry, and airway hyper-responsiveness. Information of 1-year follow-up was recorded in a part of patients who received complete cough relief after 2 months of treatment. SAD was defined as any two parameters of maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow at 50% of forced vital capacity (FEF50%) pred, and forced expiratory flow at 75% of forced vital capacity (FEF75%) pred measuring <65%.Results: SAD occurred in 73 (60.8%) patients with CVA before treatment. The patients with SAD showed a significantly longer cough duration (24.0 vs. 6.0, p = 0.031), a higher proportion of women (78.1 vs. 59.6%, p = 0.029), older mean age (41.9 vs. 35.4, p = 0.005), and significantly lower forced expiratory volume in 1 s (FEV1%) pred, FEV1/FVC, MMEF% pred, FEF50% pred, FEF75% pred, PEF% pred, and PD20 (all p < 0.01) as compared with patients without SAD. There were no significant differences in cough VAS, sputum eosinophils count, FeNO, and TIgE level between patients with SAD and those without SAD. Among 105 patients who completed 2 months of antiasthmatic treatment and repeatedly experienced spirometry measurement, 57 (54.3%) patients still had SAD, despite a significant improvement in cough VAS, sputum eosinophils, FeNO, FEF50% pred, and PEF% pred (all p < 0.01). As compared with patients without SAD, patients with SAD showed no significant differences in the relapse rate (50.0 vs. 41.9%, p = 0.483) and wheeze development rate (10.4 vs. 0%, p = 0.063) during the follow-up.Conclusions: Small airway dysfunction occurred in over half of patients with CVA and persisted after short-term antiasthmatic treatment, which showed distinctive clinical and pathophysiological features.

BackgroundThe aim of this study was to investigate differences in clinical features and HLA genotypes between adult‐onset and childhood‐onset patients with type 1 diabetes in a Chinese population.Materials and MethodsThis study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood‐onset and 458 adult‐onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood‐onset and 114 adult‐onset) were selected for HLA DR and DQ genotyping by next‐generation sequencing.ResultsAdult‐onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C‐peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood‐onset patients, adult‐onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high‐risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non‐risk) genotypes.ConclusionsAdult‐onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR‐DQ haplotypes than childhood‐onset patients, which suggested the association between less risk DR‐DQ genotypes and the less severe clinical manifestation in adult‐onset patients.

BackgroundThe AtyPical Asthma in China (APAC) cohort is a multi-center prospective, observational cohort set-up to investigate the clinical, pathophysiological features, prognosis, and mechanisms of cough variant asthma (CVA).ObjectivesTo present the characteristics of newly physician-diagnosed adults with CVA (n = 328) compared to mild-moderate classic asthma (CA, n = 206).Methods and Main ResultsCVA subjects showed a higher proportion of female (67.1 vs. 55.3%, P = 0.0084), abnormal laryngopharyngeal sensations (71 vs. 51%, p < 0.0001) than CA, but presented with near normal spirometry and higher methacholine PD20-FEV1 values [4.2 (1, 8.6) vs. 0.8 (0.4, 4.7), P < 0.0001]. Lower fractional exhaled nitric oxide (FENO) levels [38.5 (19.8, 72.5) vs. 53. (28.5, 92.2), P = 0.0019], blood eosinophil counts [0.2 (0.1, 0.4) vs. 0.3 (0.2, 0.5), P = 0.0014], and sputum eosinophils [2.3 (0.3, 8.0) vs. 12.2 (2, 34.5), p < 0.0001] were found in CVA. Despite lower total serum IgE levels in CVA, there was similar proportion of atopy in both groups. The prevalence of cough in CA was 86.4%, while CVA reported more severe cough on Visual Analog Scale, Cough Evaluation Test, and Leicester Cough Questionnaire, similar anxiety and depression scores but better asthma control scores as reflected by Asthma Control Test compared to CA. No correlation was found between cough assessment outcomes and sputum eosinophil count, blood eosinophil count, FENO, spirometry variables, or PD20-FEV1.ConclusionCough variant asthma is distinctive from classic asthma in regard to clinical features, lung function, and airway inflammation. Quality of life is badly impaired as well in spite of better asthma control scores.

Aims/hypothesis The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract