Sex and intimacy in people with severe asthma: a qualitative study.

Introduction: People with severe asthma experience unpredictable daily symptoms requiring an intense treatment regimen impacting on health-related quality of life (QoL). Sexuality contributes to this, yet there is a dearth of research exploring intimacy in people with severe asthma. We aimed to explore the patient's perception of the impact of severe asthma on intimacy, establish their information needs and their perceived role of the healthcare practitioner. Methods: We have performed a qualitative study guided by Interpretive Phenomenological Analysis. We interviewed patients diagnosed with severe asthma recruited from a dedicated clinic using purposive sampling. Interviews were audio recorded and transcribed verbatim. Using thematic analysis, the data were analysed for emergent themes. Results: The nine interviews provided unique and detailed insights into their perspectives on how living with severe asthma impinges on sexual intimacy. Four superordinate themes emerged: (1) 'Physical intimacy': including disclosure of physical limitations of severe asthma on intimacy; (2) 'Emotional intimacy': the cyclical impact of the often-negative emotional struggle of living with severe asthma on relationships; (3) 'The role of the healthcare professional': a perceived failure of healthcare professionals (HCPs) to tackle sexual intimacy in consultations and (4) 'Image of self': the reported struggle to deal with negative body image and confusion regarding changing relationship roles. Discussion: This study is the first to explore the impact of severe asthma on intimacy. We suggest an emphasis on education to raise awareness and help HCPs to address this sensitive topic in this cohort and adopt positive strategies to help improve QoL.

European consensus meeting/statement on Bronchial Thermoplasty Who? Where? How?

BACKGROUND: Bronchial Thermoplasty (BT) is a bronchoscopic treatment for severe asthma. Following research trials there remains a need to guide BT treatment in clinical practice, specifically in the fields of patient assessment, selection and positioning of BT within the range of treatment modalities, BT treatment protocols and post-BT management and follow-up. Consensus statements can bridge the gap between evidence-based medicine and real world clinical practice. METHODS: We performed a modified RAND consensus analysis using a baseline list of statements derived from ATS/ERS Guidelines on Severe Asthma, Cochrane review and UK commissioning guidance. A panel of 5 European BT experts, individually scored the statements and following a day of discussion, rescored a revised final list independently. RESULTS: An initial list of 132 statements, were independently scored. These were modified to 108 following group discussion. Consensus/total agreement was reached for 68 (63%) of the statements; 8 (7.4%) statements achieving total disagreement. For only 17 statements, could some form of consensus not be achieved. CONCLUSIONS: The consensus document could be applied to guide BT clinical practice and used to serve as a minimum acceptable level of assessment for BT, drive the development of clinical practice protocols and help define quality indicators.

Lung abscess as a complication of bronchial thermoplasty.

BACKGROUND: Bronchial thermoplasty (BT) is an emerging treatment modality for patients with difficult to treat asthma. It has been shown to be beneficial for symptom control and improves quality of life and reduces frequency of hospitalization. Safety data from the two major trials of BT indicate that patients who undergo these procedures are most likely to experience adverse respiratory events in the first six weeks post treatment. Lung abscess has never been reported as a direct complication of BT. In this case; we report a lung abscess as an immediate complication of BT, which we believe may be the first case. CASE PRESENTATION: We describe a forty three year old Caucasian female presented three days post-bronchial thermoplasty with left sided chest pain radiating to the back associated with shortness of breath, wheeze and dry cough. She had also started to feel hot and cold and generally unwell. CONCLUSION: It remains unclear why this patient developed a lung abscess so acutely post BT treatment. It is important that safety data continues to be collated and published as the procedure becomes more widely available with further long term follow-up in particular.

Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2.

Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium. Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci. Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD. Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10⁻4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD. These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking.

Intracellular secretory leukoprotease inhibitor modulates inositol 1,4,5-triphosphate generation and exerts an anti-inflammatory effect on neutrophils of individuals with cystic fibrosis and chronic obstructive pulmonary disease.

Secretory leukoprotease inhibitor (SLPI) is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca(2+)) levels which is mediated by production of inositol 1,4,5-triphosphate (IP3) in response to G-protein-coupled receptor (GPCR) stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n = 10), individuals with cystic fibrosis (CF) (n = 5) or chronic obstructive pulmonary disease (COPD) (n = 5). Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP) and interleukin(IL)-8 induced neutrophil chemotaxis (P < 0.05) and decreased degranulation of matrix metalloprotease-9 (MMP-9), hCAP-18, and myeloperoxidase (MPO) (P < 0.05). The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca(2+) flux. The described attenuation of Ca(2+) flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca(2+) flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.

Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P < 0.01); however, the levels detected were lower than in CF (P < 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P < 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P < 0.05 and P < 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB.