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Concept: Obstructive lung disease

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OBJECTIVE: Anterior chest thrusts (with the subject sitting or standing and thrusts applied to the lower sternum) are recommended by the Australian Resuscitation Council as part of the sequence for clearing upper airway obstruction by a foreign body. Lateral chest thrusts (with the victim lying on their side) are no longer recommended due to a lack of evidence. We compared anterior, lateral chest and abdominal thrusts in the generation of airway pressures using a suitable animal model. METHODS: This was a repeated-measures, cross-over, clinical trial of eight anaesthetised, intubated, adult pigs. For each animal, ten trials of each technique were undertaken with the upper airway obstructed. A chest/abdominal pressure transducer, a pneumotachograph and an intra-oesophageal balloon catheter recorded chest/abdominal thrust, expiratory air flows, airway and intrapleural pressures, respectively. RESULTS: The mean (SD) thrust pressures generated for the anterior, lateral and abdominal techniques were 120.9 (11.0), 135.2 (20.0), and 142.4 (27.3) cmH(2)O, respectively (p<0.0001). The mean (SD) peak expiratory airway pressures were 6.5 (3.0), 18.0 (5.5) and 13.8 (6.7) cmH(2)O, respectively (p<0.0001). The mean (SD) peak expiratory intrapleural pressures were 5.4 (2.7), 13.5 (6.2) and 10.3 (8.5) cmH(2)O, respectively (p<0.0001). At autopsy, no rib, intra-abdominal or intra-thoracic injury was observed. CONCLUSION: Lateral chest and abdominal thrust techniques generated significantly greater airway and pleural pressures than the anterior thrust technique. We recommend further research to provide additional evidence that may inform management guidelines for clearing foreign body upper airway obstruction.

Concepts: Sternum, Pressure, Thorax, Obstructive lung disease, Pleural cavity, Victim, Thrust, Pressure sensor

166

A 6-second spirometry test is easier than full exhalations. We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV1/FEV6) to the ratio of the FEV1/Forced vital capacity (FEV1/FVC) for the detection of airway obstruction.

Concepts: Longitudinal study, Respiratory physiology, Ratio, Spirometry, Obstructive lung disease, Vital capacity, Airway obstruction

166

BACKGROUND: There has been a large increase in treatment and in research on chronic obstructive pulmonary disease (COPD) from the common starting point of the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) study. There is currently little evidence on the degree of similarity and difference between national programmes or on the linkage between research and policy. AIMS: To review the evidence on programme development and the effectiveness gap from the UK, France, Germany, and Finland. METHODS: Visits and literature reviews were undertaken for regional centres in Lancashire, Nord-Pas de Calais, and Finland, and Eurostat data on mortality and hospital discharges were analysed. And telephone interviews in Nord-Rhein Westphalia. RESULTS: There have been very significant differences in programme development from the original GOLD starting point. The UK has national strategies but they are without consistent local delivery. The French Affection de Longue Durée (ALD) programme limits special help to at most 10% of patients and there is little use of spirometry in primary care. Germany has a more general Disease Management Programme with COPD as a late starter. Finland has had a successful 10-year programme. The results for the effectiveness gap on hospital discharges show a major difference between Finland (40.7% fall in discharges) and others (increases of 6.0-43.7%). CONCLUSIONS: The results show the need for a simpler programme in primary care to close the effectiveness gap. Such a programme is outlined based on preventing the downward spiral for high-risk patients.

Concepts: Pulmonology, Asthma, Pneumonia, Chronic obstructive pulmonary disease, Spirometry, Obstructive lung disease, Respiratory diseases, The Downward Spiral

162

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients' everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed.

Concepts: Medicine, Pulmonology, Asthma, Lung, Pneumonia, Chronic obstructive pulmonary disease, Emphysema, Obstructive lung disease

147

Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic asthma.

Concepts: Immune system, Improve, Pulmonology, Asthma, Lung, Chronic obstructive pulmonary disease, Mucus, Obstructive lung disease

146

Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists.

Concepts: Diseases and disorders, Pulmonology, Asthma, Lung, Cystic fibrosis, Chronic obstructive pulmonary disease, Respiratory system, Obstructive lung disease

40

Chronic obstructive pulmonary disease (COPD) is often misdiagnosed and inappropriately treated in many patients. COPD is a distinct disease from adult-onset asthma; however, some patients with COPD may present with several forms of airway disease described as asthma-COPD overlap (ACO). Bronchodilators and inhaled corticosteroids (ICS) both have a place in standard maintenance treatment of COPD and asthma; however, recommendations for use differ widely. In patients with COPD, long-acting bronchodilators are effective initial monotherapy treatment, while ICS monotherapy is recommended as initial treatment in patients with asthma. Clinicians need to be confident in their diagnosis to ensure that correct treatment is given, as misguided treatment decisions can result in significantly increased safety risks for patients. This review highlights the differences in diagnosis and treatment between COPD, asthma, and ACO and discusses the data supporting guideline recommendations for use of bronchodilators in COPD treatment in contrast to asthma or ACO.

Concepts: Asthma, Medical terms, Pneumonia, Chronic obstructive pulmonary disease, Spirometry, Obstructive lung disease, Bronchodilator

36

The cystic fibrosis (CF) lung microbiome has been studied in children and adults; however, little is known about its relationship to early disease progression. To better understand the relationship between the lung microbiome and early respiratory disease, we characterized the lower airways microbiome using bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants and preschoolers who underwent bronchoscopy and chest computed tomography (CT). Cross-sectional samples suggested a progression of the lower airways microbiome with age, beginning with relatively sterile airways in infancy. By age two, bacterial sequences typically associated with the oral cavity dominated lower airways samples in many CF subjects. The presence of an oral-like lower airways microbiome correlated with a significant increase in bacterial density and inflammation. These early changes occurred in many patients, despite the use of antibiotic prophylaxis in our cohort during the first two years of life. The majority of CF subjects older than four harbored a pathogen dominated airway microbiome, which was associated with a further increase in inflammation and the onset of structural lung disease, despite a negligible increase in bacterial density compared to younger patients with an oral-like airway microbiome. Our findings suggest that changes within the CF lower airways microbiome occur during the first years of life and that distinct microbial signatures are associated with the progression of early CF lung disease.

Concepts: Bacteria, Diseases and disorders, Respiratory disease, Pulmonology, Pneumonia, Cystic fibrosis, Bronchoalveolar lavage, Obstructive lung disease

31

Differences in asthma severity may be related to inflammation in the airways. The lower airway microbiota has been associated with clinical features such as airway obstruction, symptom control, and response to corticosteroids.

Concepts: Immune system, Inflammation, Asthma, Allergy, Atopy, Allergen, Corticosteroid, Obstructive lung disease

28

ABSTRACT BACKGROUND: Disease progression in chronic obstructive pulmonary disease (COPD) is associated with decline in exercise performance over time. We assessed whether tiotropium might mitigate this by determining its effect on treadmill endurance time (ET) over 2 years. METHODS: Randomized, double-blind, placebo-controlled trial of tiotropium 18 µg daily in patients with COPD (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%; postbronchodilator FEV1 < 65%). Primary endpoint: ET at 90% of baseline maximum work rate at 96 weeks. Secondary endpoints: ET at other visits, ET by smoking status, spirometry, St George Respiratory Questionnaire (SGRQ). RESULTS: 519 patients randomized (tiotropium 260, placebo 259), mean 65 years, 77% men, 34% continuing smokers, FEV1 1.25 L (44% predicted). Significantly more patients discontinued placebo: hazard ratio (95% CI) 0.61 (0.44, 0.83). Baseline ET was 301 s (improvement tiotropium/placebo: 13% overall, P = 0.009; 18% at 48 weeks, P = 0.004; 13% at 96 weeks, P = 0.106). In patients with baseline ET between 2-10 minutes (n = 404), improvement at 96 weeks was 19% (P = 0.04). Current smokers had higher ET with tiotropium vs placebo (P = 0.018). FEV1/FVC improved with tiotropium (P < 0.01). SGRQ total score at 96 weeks improved with tiotropium vs placebo by 4.03 units (P = 0.007). CONCLUSIONS: Treadmill ET was numerically greater over 2 years with tiotropium vs placebo. However, 96-week difference was not statistically significant. Spirometry and health status also improved with tiotropium over 2 years, attesting to the benefits of long-acting bronchodilator therapy.ClinicalTrials.gov: NCT00525512.

Concepts: Pulmonology, Asthma, Respiratory physiology, Chronic obstructive pulmonary disease, Spirometry, Tiotropium, Obstructive lung disease, Bronchodilator