The number of patients requiring prolonged mechanical ventilation (PMV) is increasing worldwide, placing a burden on healthcare systems. Therefore, investigating the pathophysiology, risk factors, and treatment for PMV is crucial. Various underlying comorbidities have been associated with PMV. The pathophysiology of PMV includes the presence of an abnormal respiratory drive or ventilator-induced diaphragm dysfunction. Numerous studies have demonstrated that ventilator-induced diaphragm dysfunction is related to increases in in-hospital deaths, nosocomial pneumonia, oxidative stress, lung tissue hypoxia, ventilator dependence, and costs. Thus far, the pathophysiologic evidence for PMV has been derived from clinical human studies and experimental studies in animals. Moreover, recent studies have demonstrated the outcome benefits of pharmacological agents and rehabilitative programs for patients requiring PMV. However, methodological limitations affected these studies. Controlled prospective studies with an adequate number of participants are necessary to provide evidence of the mechanism, prognosis, and treatment of PMV. The great epidemiologic impact of PMV and the potential development of treatment make this a key research field.

Background: Bronchiectasis is a chronic infectious respiratory disease with diverse causes and ethnic or geographic differences. However, few large-scale studies of its etiology have been conducted in Asia. This study aimed to determine the etiology and clinical features of bronchiectasis in Taiwan.Methods: This longitudinal cohort study investigated the etiology and clinical features of newly diagnosed non-cystic fibrosis bronchiectasis patients from January 2002 to December 2016. The clinical, functional and microbiological data of patients were retrieved from the Chang Gung Research Database, which includes seven medical facilities throughout Taiwan. The index date was the date of the first bronchiectasis diagnosis. Known diseases that were diagnosed before the index date were regarded as etiologies of bronchiectasis.Results: The cohort comprised 15,729 adult patients with bronchiectasis. Idiopathic (32%) was the most common cause, followed by post-pneumonia (24%). Other causes included post-tuberculosis (12%), chronic obstructive pulmonary disease (14%), asthma (10%), gastroesophageal reflux disease (2%) and rheumatic diseases (2%). At diagnosis, 8487 patients had sputum culture.Pseudomonas aeruginosa(5.3%) was the most common bacteria, followed by non-tuberculosis mycobacteria (3.6%),Haemophilus influenzae(3.4%) andKlebsiella pneumoniae(3.1%), but 6155 (72.1%) had negative sputum cultures. Patients with post-tuberculosis had a higher sputum isolation rate of non-tuberculosis mycobacteria thanP. aeruginosa. Patients with post-tuberculosis and post-pneumonia bronchiectasis had a higher frequency of chronic lung infection than other groups (p < 0.05). Clinical characteristics, such as gender, lung function, comorbidities and microbiology, were significantly different between idiopathic and known etiologies.Conclusions: Idiopathic, post-infection and tuberculosis constitute major bronchiectasis etiologies in Taiwan. Clinical characteristics and sputum microbiology were distinct among separate etiology phenotypes.

Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects (n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV₁) decline (<30 mL/year, n = 13) and those with a fast FEV₁ decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV₁ decline group was decreased, but that of the fast FEV₁ decline group was increased (PC₂₀, provocative concentration causing a 20% decrease in FEV₁, 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV₁ decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV₁ decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV₁ decline group (0.089 ± 0.032) was higher than that of the slow FEV₁ decline group (0.007 ± 0.001, p < 0.01). The annual FEV₁ decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV₁ showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma.

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV_1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospitalization in bronchiectasis. We highlight the importance of preventing or treating influenza infection in bronchiectasis.

Purpose: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. Methods: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. Results: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. Conclusions: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.