Regular aspirin use may reduce progression of COPD, study suggests

By Dr Deepu

Regular aspirin use was associated with a more than 50% reduction in emphysema/chronic obstructive pulmonary disease (COPD) progression in an elderly cohort over a decade in a longitudinal analysis of data from a large lung study, researchers reported.
The findings were published in the journal CHEST.
The important findings of the Study are:

*Emphysema increased 0.60 percentage points over 10 years (95% CI 0.35 to 0.94) on an average.

*Aspirin users showed slower progression of percent emphysema was compared to non-aspirin users (fully adjusted model: -0.34% per 10 years, 95% CI -0.60 to -0.08; P=0.01).

*Results were similar in ever-smokers and for doses of 81 mg and 300-325 mg. A greater magnitude effect was seen among participants with airflow limitations.

*No association was found between aspirin use and change in lung function.
The association was seen in a wide range of aspirin usage, and was greatest in older study participants with significant airflow obstruction.
These findings, along with supportive results in animals, suggest that further study of aspirin and platelet activation in emphysema may be warranted.
They mentioned that platelet activation reduces pulmonary microvascular blood flow and contributes to inflammation, which has been shown to be important in the pathogenesis of COPD/emphysema.

The hypothesis of the Study was that regular use of aspirin, a platelet-inhibitor, would be associated with slower progression of emphysema-like lung on computed tomography (CT), and slower decline in lung function. Percent emphysema assessment was limited to the lower two-thirds of the lungs and baseline differences in emphysema were significant among aspirin users and non-users, with users having a greater percent emphysema.
The study used data from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which assessed the percentage of emphysema-like lung below-950 Hounsfield units ("percent emphysema") on cardiac and full-lung CT. There were 4,257 participants from the MESA Lung Study. Their mean (±SD) age was 61±10 years, 54% were ever-smokers, and 22% used aspirin regularly.

Spirometry was conducted during 2004-2007 and repeated in 2010-2012 in accordance with American Thoracic Society-European Respiratory Society guidelines following the MESA Lung protocol.
The airflow obstruction was defined as pre-bronchodilator FEV₁/FVC <0.70 and restrictive ventilatory defect as FVC<lower limit of normal and FEV₁/FVC≥0.7.
Regular aspirin use included 3 or more days per week and mixed effects models adjusted for demographics, anthropometry, smoking, hypertension, ACE-inhibitor use, C-reactive protein, sphingomyelins, and scanner factors.
Results were similar after propensity score weighting and when the exposure was defined as any aspirin use at baseline, and there was no evidence for effect modification associated with age and race/ethnicity.
Results were also similar after adjustment for inhaler, NSAID, COX-2 inhibitor, ADP-receptor inhibitors, statin, and diuretic use.
This is the first study of which we are aware to show an association between aspirin use and longitudinal progression of percent emphysema.
Prior studies have found platelet-receptor related genes serotonin receptor 4 (HTR4), von Willebrand factor (VWF) and its platelet-receptor, GP1BA, to be associated with FEV₁ and COPD. Additionally, platelet factor 4  increased emphysema when added to a neutrophil elastase animal model of emphysema, and platelet activation was found to be greater in COPD compared to controls, and during exacerbation.

Leaving Bedroom Door Or Window Open May Be Linked To Better Sleep Quality, Study Suggests

By Dr Deepu

A research from Netherlands suggests “leaving a bedroom door or window open may help people sleep better.” Researchers found that “open windows and doors helped reduce carbon dioxide levels and improve ventilation and air flow, which was related to better sleep quality for the healthy young adults in the study.” The findings were published in the journal Indoor Air.
For one night of the study, 17 volunteers slept with an open window or internal door. On another night, the windows and door to the room were kept closed. In the meantime, Mishra and colleagues monitored carbon dioxide levels, temperature, background noise and humidity. The study participants were asked not to drink alcoholic beverages or caffeinated drinks, which could influence sleep. They each slept alone, and the bedroom layout with furniture arrangement was kept consistent.
For measuring sleep quality, participants wore an armband that measures skin temperature, heat flux, bed temperature and skin moisture levels. They also wore a sensor that tracked their movements at night, including indications of restlessness.
Closed environments tended to have less background noise – but they also had significantly higher carbon dioxide levels, which indicated lower ventilation levels.
Open conditions were slightly cooler than closed, although humidity levels were similar across settings, according to the report in the journal Indoor Air.
Notably, carbon dioxide levels were lower when windows or doors were open.
Overall, skin temperature and the bed temperature were higher in closed conditions than open conditions. The number of awakenings and sleep efficiency improved as carbon dioxide levels decreased.
A limitation of the study is that the motion sensor often slipped off the sleepers at night.

Mounier - Kuhn Syndrome

By Dr Deepu

Mounier-Kuhn syndrome is characterized by distinct tracheobronchial dilation that is due to atrophy of the muscular and elastic tissues in the trachea and main bronchial wall. It is more common in men and is typically diagnosed in the 3rd or 4th decades of life. The clinical presentation varies widely, from minimal disease in which lung function is preserved to severe respiratory failure and death. Involvement occurs at different levels, from the trachea down to the 4th bronchial branch.Although its cause is not fully known, tracheobronchomegaly is reportedly linked to familial susceptibility and is perhaps inherited through an autosomal recessive mechanism. Cases are often sporadic.

Mounier-Kuhn syndrome has 3 subtypes. In type 1, there is a slight symmetric dilation in the trachea and main bronchi. In type 2, the dilation and diverticula are distinct. In type 3, diverticular and saccular structures extend to the distal bronchi. The main problems associated with this disease are ineffective cough consequent to pathologic dilation in the tracheobronchial tree and the impairment of mucociliary activity. These cause difficulty in expectorating secretions and lead to recurrent LRTIs.The symptoms of Mounier-Kuhn syndrome are nonspecific. In the absence of infection, the disease can develop asymptomatically. Bronchiectasis and LRTIs are clinically prominent, and recurrent pneumonia and fibrosis can develop.

Diagnosis is often made by using CT, through which abnormally large air passages are detected. In adults, the diagnostic criteria are diameters of the trachea, >30 mm; of the right main bronchus, 20 mm; and of the left main bronchus, 18 mm.Upon pulmonary function testing, decreased bronchial flow speed, increased tidal volume, and dead spaces may be observed. Bronchoscopy can detect the pathologic processes that affect the tracheobronchial structures—specifically, dilation in the trachea and main bronchi during inspiration, and constriction and even collapse during expiration and coughing.

Connective-tissue diseases, ataxia-telangiectasia, ankylosing spondylitis, Ehlers-Danlos syndrome, Marfan syndrome, Kenny-Caffey syndrome, Brachmann-de Lange syndrome, and cutis laxa (elastolysis) are also associated with secondary tracheobronchial enlargement.All of these conditions should be considered in the differential diagnosis.

Asymptomatic patients require no specific treatment. Cessation of smoking is highly beneficial, as is minimizing exposure to industrial and occupational irritants and pollutants. In symptomatic patients, therapy is supportive but is limited to respiratory physiotherapy for clearing secretions and to antibiotic use during infectious exacerbations.Although tracheal stenting has been helpful in severe cases, surgery is rarely performed because of the diffuse nature of the disease. Lung transplantation provided no proved benefit in regard to the risk of morbidity and death.

Schwartz M, Rossoff L. Tracheobronchomegaly. Chest 1994; 106(5):1589–90. [PubMed]

Mounier-Kuhn P. Dilatation de la trachee: constatations radiographiques et bronchoscopiques. Lyon Med 1932;150:106–9.

 Damgaci L, Durmus S, Pasaoglu E. Mounier-Kuhn syndrome (tracheobronchomegaly). Tanisal ve Girisimsel Radyoloji 2002;8(1):165–6.

Dunne MG, Reiner B. CT features of tracheobronchomegaly. J Comput Assist Tomogr 1988;12(3):388–91.[PubMed]

Noori F, Abduljawad S, Suffin DM, Riar S, Pi J, Bennett-Venner A, et al. Mounier-Kuhn syndrome: a case report. Lung 2010;188(4):353–4.[PubMed]

Menon B, Aggarwal B, Iqbal A. Mounier-Kuhn syndrome: report of 8 cases of tracheobronchomegaly with associated complications. South Med J 2008;101(1):83–7. [PubMed]

Ghanei M, Peyman M, Aslani J, Zamel N. Mounier-Kuhn syndrome: a rare cause of severe bronchial dilatation with normal pulmonary function test: a case report. Respir Med 2007; 101(8):1836–9. [PubMed]

Noninvasive ventilation may be beneficial for patients with acute hypercapnic respiratory failure during COPD exacerbations, data indicate

By Dr Deepu

A review of a recent meta-analysis published in the Annals of Emergency Medicine indicates that noninvasive ventilation provides benefit in patients with acute hypercapnic respiratory failure during chronic obstructive pulmonary disease (COPD) exacerbations, reducing mortality and the need for mechanical ventilation.

Authors also added that noninvasive ventilation also may improve length of hospital stay, serum pH, and oxygen partial pressure. The meta-analysis included 17 randomized controlled trials with 1264 patients.

The review authors noted that severe COPD is characterized by hyperinflation, airway obstruction, and decreased respiratory muscle function. In this setting, exacerbation can result in hypercarbic respiratory failure. Usual care includes controlled oxygenation, bronchodilators, corticosteroids, and antibiotics. If these interventions fail, intubation is initiated.

Limitations of the meta-analysis include the variability of usual care and noninvasive ventilation duration in the studies, the potential for publication bias regarding the need for intubation, and low heterogeneity for both mortality and the need for intubation.

The meta-analysis provides strong evidence that noninvasive ventilation reduces mortality, the need for intubation, and hospital length of stay in patients with acute hypercapnic respiratory failure during an acute exacerbation of COPD. The findings support a trial of noninvasive ventilation in patients with a pH of less than 7.30 before proceeding with intubation.

Sputum eosinophil count may predict severity of COPD in smokers, research suggests

- Blood eosinophil count alone not predictive in SPIROMICS cohort
By Dr Deepu

Investigators found that “sputum eosinophil count proved to be a better biomarker of chronic obstructive pulmonary disease (COPD) severity and exacerbations than blood eosinophil count alone in a study involving a large group of smokers with a broad range of airflow obstruction severities.” The investigators found, “in the analysis...blood eosinophil count as a single biomarker was not predictive of sputum eosinophils and was not associated with disease severity or exacerbations unless combined with sputum count.” But, “increased sputum eosinophil inflammation...was found to be associated with more severe COPD, decreased lung function, worse emphysema and air trapping, and a greater likelihood of exacerbations.” The findings were published in The Lancet Respiratory Medicine

Patients enrolled in SPIROMICS had a smoking history of at least 20 pack-years and were recruited from six clinical sites and subsites in the U.S. between November 2010 and spring 2015. All had complete baseline blood cell counts, and a subset had acceptable sputum counts.

A total of 2,499 participants with available blood counts were stratified by mean blood eosinophil count: 1,262 patients with low (<200 cells per μL) and 1,237 with high (≥200 cells per μL) blood eosinophil counts.

A total of 827 patients were eligible for stratification by mean sputum eosinophil percentage including 656 with low (<1.25%) and 171 with high (≥1.25%) sputum eosinophil percentages. Analyses were also conducted involving blood eosinophil cutoffs of 300 cells/μL and sputum eosinophil cutoffs of 2%.

The high sputum eosinophil group had significantly lower median forced expiratory volume in 1 second (FEV)₁ percentage predicted than the low sputum eosinophil group, both before (65.7% [IQR 51.8-81.3] versus 75.7% [59.3-90.2], P<0·0001) and after (77.3% [63.1-88·5] versus 82.9% [67.8-95.9], P=0.001) bronchodilation.

Qualitative computed tomography (CT) density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than in the low sputum eosinophil group and exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (P=0.002).
The main findings of the study are:

FEV₁ percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups

The high blood eosinophil group had slightly increased airway wall thickness (0.02 mm difference, P=0·032), higher St George Respiratory Questionnaire symptom scores (P=0.037), and increased wheezing (P=0.018, but no evidence of an association with COPD exacerbations (P=0.35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, BMI, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage

Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0.64, P<0.0001), but with a high false-discovery rate of 72%

With the higher blood eosinophil cutoff of 300 cells/μL, no significant differences were seen between the high and low count groups. But at the higher 2% sputum eosinophil cutoff, significant differences were seen between the low and high groups for all categories of COPD exacerbations.

The ECLIPSE study reported that 1,483 patients stratified by blood eosinophil counts did not have different numbers of COPD exacerbations in the previous year. Researchers noted that higher blood eosinophils are not associated with COPD exacerbations except when combined with increased sputum eosinophils or with other characteristics, such as a previous history of exacerbations. In the SPIROMICS cohort, higher sputum eosinophil counts alone are associated with exacerbations even in mild to moderate COPD