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RATIONALE: We have previously shown increased expression of the Frizzled-8 receptor of the Wingless/integrase-1 (WNT) signalling pathway in COPD. Here, we investigated if the Frizzled-8 receptor has a functional role in airway inflammation associated with chronic bronchitis. METHODS: Acute cigarette-smoke-induced airway inflammation was studied in wild-type and Frizzled-8-deficient mice. Genetic association studies and lung expression quantitative trait loci (eQTL) analyses for Frizzled-8 were performed to evaluate polymorphisms in FZD8 and their relationship to tissue expression in chronic bronchitis...

Mechanical ventilation has a long and storied history, but until recently the process required little from the emergency physician. In the modern emergency department, critically ill patients spend a longer period under the care of the emergency physician, requiring a greater understanding of ventilator management. This article serves as an introduction to mechanical ventilation and a user-friendly bedside guide.

Since its introduction into the management of the acute respiratory distress syndrome, mechanical ventilation has been so strongly interwoven with its side effects that it came to be considered as invariably dangerous. Over the decades, attention has shifted from gross barotrauma to volutrauma and, more recently, to atelectrauma and biotrauma. In this article, we describe the anatomical and physiologic framework in which ventilator-induced lung injury may occur. We address the concept of lung stress/strain as applied to the whole lung or specific pulmonary regions...

Synthetic glucocorticoids are among the most commonly used prescription medicines. Nevertheless, their clinical efficacy is accompanied by dose- and indication-limiting acute and chronic adverse effects. Intrinsic or acquired resistance to glucocorticoid actions may also limit clinical efficacy. In chronic inflammatory conditions there has been a considerable focus on understanding mechanism(s) of resistance in cells with a primary immune and/or inflammatory function. However, it has become increasingly accepted that a substantial part of the efficacy of glucocorticoid treatments derives from actions on 'structural' cell types (smooth muscle, fibroblasts, epithelia)...

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Guidelines for asthma management focus on the use of combination inhaled treatment with corticosteroids and longacting β-agonists for symptomatic asthma. In more severe disease, other drugs such as leukotriene blockers and slow-release oral theophylline are added, with oral corticosteroids and anti-immunoglobulin E treatment with omalizumab for the most severe cases of asthma. Once-daily longacting β-agonists and inhaled corticosteroids are being developed. Longacting muscarinic antagonists might also provide additive benefit...

Steroid-resistant asthma (SRA) refers to patients with symptoms consistent with asthma who show very poor or no response at all to high doses of inhaled or even of systemic corticosteroids. The current article reviews the SRA related literature focusing on the problems associated with the definition of SRA (especially its association with difficult to control, or severe asthma), its various phenotypes, its molecular basis, and the potential treatment options. The article also discusses the limitations of some of the key criteria used for the determination of SRA and proposes a modified set of criteria that are more applicable to children...

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 μg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone...

Psychological morbidity is common in chronic respiratory diseases. The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed. Consecutive COPD patients (GOLD stage I-IV, 40-75 years old) were enrolled in a multicentre, cross-sectional cohort study. Diagnosis of depression was ascertained through clinical records. Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated...

The 6-minute walk distance (6MWD) is one of the most commonly used measures of functional capacity in lung cancer, however, the minimal important difference (MID) has not been established. The aims of this exploratory study are, in lung cancer, to estimate (1) the MID of the 6MWD and (2) relationship between 6MWD, demographic and disease-related factors. Fifty-six participants with stage I-IV lung cancer completed the 6MWD prior to treatment and 10 weeks later. No exercise intervention occurred. Additional measures included European Organization for Research and Treatment of Cancer questionnaire (EORTC-QLQ-C30) and questionnaires assessing function, physical activity and symptoms...

OBJECTIVE: To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease...

Birt-Hogg-Dubé syndrome is characterized by clinical manifestations such as hamartomas of the skin, renal tumors and lung cysts with spontaneous pneumothoraces. Patients with Birt-Hogg-Dubé syndrome may present with only multiple lung cysts. We report the chest computerized tomography (CT) features of three patients with Birt-Hogg-Dubé syndrome. Each patient had multiple lung cysts of various sizes according to chest CT evaluation, most of which were located in lower lobes and related to pleura...

Pulmonary capillary hemangiomatosis is a rare cause of pulmonary hypertension characterized by extensive proliferation of pulmonary capillaries within alveolar septae. Clinical presentation is nonspecific and includes dyspnea, cough, chest pain, and fatigue. Radiology shows diffuse centrilobular ground-glass opacities. Pulmonary capillary hemangiomatosis is clinically and radiographically indistinguishable from peripheral venoocclusive disease, making microscopic diagnosis essential. Histologically, pulmonary capillary hemangiomatosis shows an abnormal proliferation of small, thin-walled capillaries that expand the alveolar septae...

BACKGROUND: Depression is very prevalent in COPD and may be associated with poor clinical outcomes. METHOD: This was a multicenter, cross-sectional study aimed at evaluating the prevalence of depression and moderate to severe depression in COPD. Depressive symptoms were evaluated with the Beck's Depression Inventory. The COPD assessment test (CAT) and the EuroQoL-5 dimensions (EQ-5D) questionnaires were used to evaluate health-related quality of life (HRQoL). Severity of COPD was assessed with the BODEx index and physical activity was estimated by the mean self-declared time walked per day...

Influenza A virus is a pathogen that is feared for its capacity to cause pandemics. In this review, we illustrate the clinical evidence which support the theory that bacterial co-infection is a considerable risk factor for exacerbated disease during pandemic and seasonal influenza, including infection with influenza B viruses. We provide an overview of the multiple and diverse mechanisms that help explain how influenza creates an opportunity for replication of secondary bacterial infections. Influenza vaccines and pneumococcal vaccines are widely used and often in overlapping target groups...

BACKGROUND: The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD). We previously developed a score ('2008 score', based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs). External validity of this score remained to be assessed. OBJECTIVES: To test the predictive properties of the '2008 score' in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance...

Clinical decisions should be based on the totality of the best evidence and not the results of individual studies. When clinicians apply the results of a systematic review or meta-analysis to patient care, they should start by evaluating the credibility of the methods of the systematic review, ie, the extent to which these methods have likely protected against misleading results. Credibility depends on whether the review addressed a sensible clinical question; included an exhaustive literature search; demonstrated reproducibility of the selection and assessment of studies; and presented results in a useful manner...

BACKGROUND: Aspiration pneumonia is a leading cause of death in people with Parkinson disease (PD). The pathogenesis of these infections is largely attributed to the presence of dysphagia with silent aspiration or aspiration without an appropriate cough response. The goal of this study was to test reflex cough thresholds and associated urge-to-cough (UTC) ratings in participants with PD with and without dysphagia. METHODS: Twenty participants with PD were recruited for this study...

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone...