Background As a typical “united airway” disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS. Methods This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed. Results Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV1) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV1% predicted and body mass index. Cutoff values of FEV1% predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 109/L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients. Conclusions Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.

The aim of the study was to explore the functional and structural changes of the diaphragm and underlying mechanisms in response to 12 or 24 weeks of cigarette smoke (CS) exposure in rats. Materials and Methods: Rats were exposed to CS to develop a COPD model and the rats exposed to room air served as a control group. Rats were randomly divided into four groups: CS12W, CON12W, CS24W, and CON24W. Pulmonary function, lung histopathology, and the contractile properties and ultrastructure of diaphragm muscle were examined in these rats. The changes of transcriptomic profiling of diaphragm muscle were further compared between CS and control rats by the RNA Seq. Results: Both CS groups showed lower FEV 0.3 /FVC, elevated mean linear intercept (MLI), and reduced mean alveolar numbers (MAN) vs the control groups. The fatigue index (FI) of the diaphragm muscle from the CS12W group, but not CS24W, was significantly increased. Conversely, the force-frequency curves of the diaphragm muscle from the CS24W group, but not CS12W group, were significantly decreased. Consistently, mitochondrial number density (N A) and volume density (Vv) were increased in the CS12W diaphragm muscle, while being decreased in the CS24W group. Furthermore, the diaphragm transcriptomic profiling results showed that genes regulating cell proliferation and energy metabolic activity were un-regulated and genes regulating protein degradation were down-regulated in the CS12W diaphragm, while CS24W diaphragm showed opposite changes. Conclusion: These observations suggested a transition of diaphragm muscle from initial compensatory to decompensatory changes in function, structure, and gene expression during the development of COPD.

Background: Cigarette smoking (CS) is one of the greatest risk factors for the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Although CS cessation is beneficial in preventing COPD progression, the effects of cessation on the diaphragm are unknown, as are the CS-induced mitochondrial changes in the diaphragm during COPD and CS-cessation. In this study, we examined the alterations in mitochondrial morphology and homeostasis, as well as changes in diaphragm contractility during CS exposure and after cessation.Methods: Rats were randomly divided into control, CS-exposure, and CS-cessation groups, including 3-month CS (S3), 6-month CS (S6), 6-month CS followed by 3 months cessation (S6N3), and age-matched control groups. The histological and functional changes in the lungs were examined to evaluate the CS-induced COPD model. The alterations in the diaphragm were further investigated, including contractile properties, the ultrastructure, and the expression of markers of mitochondrial homeostasis.Results: CS exposure caused histological disruption and functional depression in the lungs, and CS cessation failed to result in a significant recovery. CS induced a significant decline in diaphragmatic muscle contractility, accompanied with sever contractile dysfunction in extensor digitorum longus muscles, which was recovered after 3-month CS cessation. CS exposure in parallel disrupted the mitochondrial morphology in diaphragmatic muscle, including decreases in volume density and number density in the S6 group, which was significantly alleviated in the S6N3 group. The mitochondrial quality control was likely depressed in the S6 group, as indicated by the downregulation of Pink1 and Mfn1, markers for mitophagy and mitochondrial fusion/fission. Interestingly, the Mfn1 protein level was recovered after smoking cessation in the S6N3 group.Conclusions: Smoking cessation eased CS-induced diaphragmatic dysfunction and mitochondrial deregulation, but not the adverse changes in pulmonary structure. These diaphragmatic muscle changes are likely associated with deregulated mitochondrial homeostasis, including mitophagy and mitochondrial fusion/fission.