Respiratory effects of insulin sensitisation with metformin: a prospective observational study.

The mechanism for the association between diabetes mellitus and lung function impairment is unknown, as are any respiratory effects of antidiabetic agents. We aimed to assess whether treatment with metformin, an oral insulin-sensitising agent, improved lung function or symptoms in individuals with COPD and glucose intolerance. A prospective open-label observational study was conducted. Participants with moderate or severe COPD, BMI > 25 kg/m(2), and type 2 diabetes mellitus or impaired glucose tolerance took metformin twice daily for 6 months. Clinical outcomes included St George's Respiratory Questionnaire (SGRQ), transition dyspnoea index, and incremental shuttle walk test. Physiological outcomes including pulmonary function tests, exhaled nitric oxide, respiratory mouth pressures and handgrip strength. In total, 17 participants completed the study. SGRQ score improved by a median of 5 points, and TDI scores improved by 2 points. Inspiratory mouth pressures increased by 7.5 cmH2O. There were trends to improvements in hyperinflation, gas trapping and shuttle walk distance. Spirometry and exhaled nitric oxide were unchanged. In this proof-of-concept study, metformin was associated with improved dyspnoea and health status in COPD, possibly related to increased inspiratory muscle strength. These and other endpoints should be examined in a definitive study.

Chronic obstructive pulmonary disease in non-smokers: a case-comparison study.

BACKGROUND: COPD is often regarded as a smoker's disease. In fact, up to 50% of COPD could be attributable to other causes. Relatively little is known about COPD among nonsmokers, and this group is usually excluded from studies of COPD. METHODS: In this cross-sectional case-comparison study, smokers and nonsmokers aged over 45 with COPD (post-bronchodilator FEV1 ≤ 70% predicted, FEV1/FVC ratio < 0.7) were recruited from specialist outpatient clinics and from primary care. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, formal lung function testing and high resolution CT. RESULTS: 48 nonsmokers and 45 smokers participated. Asthma was nearly universal among nonsmokers and was the commonest identifiable cause of COPD in that group. Nonsmokers also exhibited a high prevalence of objective eosinophilic inflammation (raised ENO and eosinophil counts, positive skinprick tests). Smokers had more severe airflow obstruction, but respiratory symptom prevalences were similar between groups. Nonsmokers reported greater lifetime burdens of respiratory disease. Nonsmokers' HRCT results showed functional small airways disease, with no significant emphysema in any subject. Previously undiagnosed bronchiectasis was common in both groups (31% and 42%). CONCLUSIONS: Asthma is a very common cause of COPD among nonsmokers. Radiological bronchiectasis is common in COPD; the clinical significance of this finding is unclear.

Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis. METHODS: We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. FINDINGS: 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108). INTERPRETATION: Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year. FUNDING: Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

Fixed airflow obstruction among nonsmokers with asthma:a case-comparison study.

BACKGROUND: Airflow obstruction in asthma is usually reversible, but fixed obstruction develops in some individuals. Little is known about risk factors for development of fixed airflow obstruction in nonsmokers with asthma. METHODS: This case-comparison study recruited nonsmokers aged over 45 years with physician-diagnosed asthma from specialist outpatient clinics and primary care. Two age-matched groups were recruited on the basis of spirometry: anobstructed group (post-bronchodilator FEV(1) ≤ 70% predicted, FEV1/FVC ratio < lower limit of normal) and a control group with normal lung function. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, and formal lung function testing. RESULTS: Thirty-four obstructed subjects and 40 controls participated in the study. Obstructed subjects exhibited greater evidence of systemic inflammation, abnormal glucose homeostasis, and central obesity than controls. Obstructed subjects reported longer duration of asthma, and childhood respiratory infection was commoner in that group. Metabolic syndrome prevalence was similar between groups, but several features of insulin resistance were associated with reduced FEV(1). Cough and sputum were common among controls. CONCLUSIONS: Risk of fixed airflow obstruction may correlate with lifetime asthma duration. Individuals with coexisting asthma and fixed airflow obstruction have heightened systemic inflammation. A variety of chronic respiratory symptoms are common among "healthy" nonsmokers with asthma.

Influence of mediterranean diet on asthma symptoms, lung function, and systemic inflammation: a randomized controlled trial.

OBJECTIVE: The rapidly increasing prevalence of asthma in developed countries suggests an environmental cause. The benefits of Mediterranean diet (MD) in cardiovascular disease have been tentatively attributed to its anti-inflammatory properties. Asthma is an inflammatory disease and MD is associated with reduced asthma risk in epidemiological studies, but there are no reported interventional studies of MD in asthma. METHODS: In this 12-week open-label randomized trial, 38 adults with symptomatic asthma were allocated to high-intervention (HI), low-intervention (LI), and control groups. The first two groups were encouraged to adopt an MD and received multiple consultation sessions with a nutritionist, written advice, and vouchers for the purchase of appropriate foods. Food frequency questionnaires, asthma control questionnaires, asthma-related quality of life questionnaires (AQLQs), and spirometry were completed at the beginning and at the end of the study. RESULTS: The MDt score increased in the HI group (p < .001), indicating successful alteration of dietary behavior. Statistically, nonsignificant improvements were seen in spirometry and several AQLQ subdomains in the two intervention groups. No changes were seen in the asthma control or in inflammatory markers. CONCLUSIONS: The trial intervention has successfully altered the dietary behavior among adults with asthma. Small but consistent improvements were seen in quality of life and spirometry among the intervention group. The use of the MD to treat asthma is feasible and warrants evaluation in a larger study, powered to examine clinical endpoints.

Necrotizing Fasciitis in the Immediate Post-Operative Period Following Resection and Free Flap Reconstruction for Oral Cancer.

Necrotising fasciitis (NF) is a rapidly spreading bacterial infection of the fascial planes and can be fatal if is not treated urgently. Here, we present the case of a 65-year-old female, with oral squamous cell carcinoma, treated surgically with curative intent. On the second post-operative day from a mandibulectomy, selective neck dissection and reconstruction with a fibula free flap, she developed rapidly progressing NF, at the surgical site.

The psychological sequelae of maxillofacial trauma: a scoping review of the literature.

Managing the physical sequelae of facial trauma is routine for the maxillofacial surgeon. However, managing the psychological consequences is more challenging. The often violent mechanism of injury, changes in appearance, altered self-perception, and self-confidence can significantly impact daily life. This review summarises the literature regarding post-traumatic stress disorder (PTSD) and facial trauma, highlighting evidence to guide clinical practice. PubMed and MEDLINE were searched for relevant keywords and MeSH headings. Articles between 2000-2022 were independently reviewed by two authors. Articles were excluded if the full text was not available in English, did not relate to facial trauma, or was not related to PTSD/psychological sequelae. A total of 211 articles were retrieved. The most common reasons for exclusion were papers not reporting psychological outcomes (n = 68) or not relating to facial trauma (n = 35). Articles were sub-categorised to enable evaluation of key themes. Categories included children and adolescents, cross sectional, longitudinal studies, and interventional studies. Whilst there were potential confounders such as socioeconomic factors, overall, patients who had experienced facial trauma (regardless of the mechanism of injury) had an increased risk of PTSD and anxiety/depression. PTSD following facial injury is increasingly recognised as an important issue. A robust evidence base is desirable to inform clinical practice and provide holistic care to often vulnerable patients. Identifying those at increased risk of negative psychological sequelae is essential. We have appraised the literature relevant to OMFS trauma clinicians.

Endoscopic lung volume reduction effectively treats acute respiratory failure secondary to bullous emphysema.

Emphysema often affects the lungs in a heterogeneous fashion, and collapse or removal of severely hyperinflated portions of lung can improve overall lung function and symptoms. The role of lung volume reduction (LVR) surgery in selected patients is well established, but that of non-surgical LVR is still being defined. In particular, use of endobronchial LVR is still under development. This case report describes a 48-year-old non-smoker with severe bullous emphysema complicated by acute hypercapnic respiratory failure, who was successfully treated by endobronchial valve placement while intubated in an intensive care unit.

Pulmonary fibroblasts from COPD patients show an impaired response of elastin synthesis to TGF-ß1.

Insufficiency of tissue repair by pulmonary fibroblasts may contribute to the decrease in elastic fibres in chronic obstructive pulmonary disease (COPD). In this study, the repair function of COPD fibroblasts was assessed by examining the response to transforming growth factor (TGF)-ß1. Primary pulmonary fibroblasts were cultured from lung tissue of COPD patients and smoking control subjects. Cellular proliferation was measured with Alamar Blue reduction method. Levels of tropoelastin mRNA and soluble elastin was measured using real-time RT-PCR and Fastin elastin assay respectively. The percentage of increase in proliferation and elastin production after TGF-ß1 (1 ng/ml) treatment was calculated for fibroblasts from each subject. COPD fibroblasts showed slower proliferation than control fibroblasts, and a reduced response to TGF-ß1 stimulation. The promotive effect of TGF-ß1 on elastin synthesis in control fibroblasts was significantly diminished in fibroblasts from COPD patients. Our findings indicate that COPD lung fibroblasts have a significantly decreased response to TGF-ß1 in terms of proliferation and elastin production.