Airway and Systemic Immunoglobulin Profiling and Immune Response in Adult Asthma.

INTRODUCTION: Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. METHODS: Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. RESULTS: There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. CONCLUSION: This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.

Current therapies for gastro-oesophageal reflux in the setting of chronic lung disease: state of the art review.

The inter-relationship between chronic respiratory disease and reflux disease in the airway reflux paradigm is extremely complex and remains poorly characterised. Reflux disease is reported to cause or contribute to the severity of a number of respiratory tract diseases including laryngeal disorders, sinusitis, chronic cough, asthma, COPD, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis and bronchiolitis obliterans post lung transplant. It is now appreciated that reflux disease is not simply caused by liquid acid reflux but rather by a variety of chemical refluxates originating from the stomach and duodenum due to a number of different mechanisms. Reflux disease can be challenging to diagnose, particularly proving its role in the causation of direct respiratory epithelial damage. Significant advances in oesophageal assessment and gastric biomarkers have emerged in recent years as our understanding increases. There are a number of treatments available for reflux disease, both medical and surgical, but there is a paucity of large randomised trials to evaluate their efficacy in the setting of chronic respiratory disease. Everyday clinical practice, however, informs us that treatment failure in reflux disease is common. This clinical review summarises associations between reflux disease in the setting of chronic respiratory diseases and examines available evidence regarding potential therapeutic strategies.

The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity.

BACKGROUND: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. METHODS: Sixty-nine patients characterized by asthma severity (GINA) and level of control (ACQ-7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus-specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. RESULTS: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL-4, IL-6, IL-10, IL-13 and TNF-α correlated with BAL fungal presence, while plasma IL-17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL-6 and BAL IL-13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. CONCLUSIONS: Fungi were present in a large proportion of our asthmatic patients' airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.

Post-tuberculosis mycetoma: bronchoscopic removal.

A 76-year-old male non-smoker presented to our institution with cough and haemoptysis. He had been treated for cavitatory pulmonary Mycobacterium tuberculosis of the right upper lobe 10 years previously. Chest radiograph and subsequent computed tomography (CT) of the chest demonstrated a right upper cavity containing a mass suspicious for mycetoma. Flexible bronchoscopy under conscious sedation demonstrated a mass obstructing the anterior segment of the right upper lobe. The abnormality was subsequently removed using a flexible endobronchial cryoprobe. Histopathological analysis demonstrated abundant fungal organisms morphologically consistent with Aspergillus species. Microbiological culture of the bronchoalveolar lavage (BAL) from the cavity isolated both Aspergillus fumigatus and Staphylococcus aureus. The patient was commenced on the anti-fungal drug posaconazole and received a course of flucloxacillin. Three months later, there was no endobronchial obstruction and lavage of the affected cavity again isolated Staphylococcus aureus without Aspergillus species. Repeat thoracic CT and flexible bronchoscopy demonstrated no further re-occurrence of the mycetoma at 3 months.

The Potential Role of Aspiration in the Asthmatic Airway.

BACKGROUND: Many people with asthma remain suboptimally controlled despite current treatments. Reasons include comorbidities that could aggravate asthma, including gastroesophageal reflux. We aimed to investigate whether aspiration occurs in patients with asthma and, if so, does it correlate with asthma control? METHODS: Patients had Asthma Control Questionnaire 7 (ACQ-7), fractional exhaled nitric oxide, and spirometry performed to characterize their level of asthma control. Barium swallow with provocation was performed to assess for predisposition to aspiration. Patients underwent bronchoscopic investigation, with BAL pepsin measured as a marker of aspiration. RESULTS: Seventy-eight patients stratified by disease severity (Global Initiative for Asthma) into mild (35.8%), moderate (21.7%) and severe (42.3%) were studied. Pepsin was detectable in BAL in 46/78 (58.9%). There were no differences between pepsin levels in patients with different disease severity. Furthermore, no significant associations were seen between pepsin level and measures of asthma control, FEV1, ACQ-7 or exacerbation frequency. Similarly no associations were found with adjustments for smoking history, BMI, proton pump inhibitor use, eosinophil count or IgE. When stratified into eosinophilic or neutrophilic asthmatic populations on the basis of BAL, there was no relationship to detected pepsin concentrations. A positive barium swallow (seen in 33/60 patients) did not correlate with BAL pepsin level and we found no significant association between barium swallow result and ACQ-7, Global Initiative for Asthma, exacerbation frequency or FEV1 using either univariate or multivariate analyses. CONCLUSIONS: This study suggests that the importance of aspiration on current asthma symptom control and exacerbation rate may be overstated. However, this study did not address the role of aspiration and future risk of exacerbation.