W.G. Flight

Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis

Background Viral respiratory infection (VRI) is a common cause of pulmonary exacerbations in children with cystic fibrosis (CF). The importance of VRI in adult CF populations is unclear. Objective To determine the incidence and clinical impact of VRI among adults with CF. Methods One hundred adults with CF were followed up prospectively for 12 months. Sputum, nose swabs and throat swabs were collected every 2 months and at onset of pulmonary exacerbation. PCR assays for adenovirus, influenza A&B, human metapneumovirus, parainfluenza 1–3, respiratory syncytial virus and human rhinovirus were performed on each sample. Symptom scores, spirometry and inflammatory markers were measured at each visit. Results One or more respiratory viruses were detected in 191/626 (30.5%) visits. Human rhinovirus accounted for 72.5% of viruses. Overall incidence of VRI was 1.66 (95% CI 1.39 to 1.92) cases/patient-year. VRI was associated with increased risk of pulmonary exacerbation (OR=2.19; 95% CI 1.56 to 3.08; p<0.001) and prescription of antibiotics (OR=2.26; 95% CI 1.63 to 3.13; p<0.001). Virus-positive visits were associated with higher respiratory symptom scores and greater C-reactive protein levels. Virus-positive exacerbations had a lower acute fall in FEV1 than virus-negative exacerbations (12.7% vs 15.6%; p=0.040). The incidence of exacerbations, but not VRI, was associated with greater lung function decline over 12 months (−1.79% per pulmonary exacerbation/year; 95% CI −3.4 to −0.23; p=0.025). Conclusion VRI is common in adults with CF and is associated with substantial morbidity. Respiratory viruses are a potential therapeutic target in CF lung disease.

Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis

ABSTRACT Respiratory infection in cystic fibrosis (CF) is polymicrobial, but standard sputum microbiology does not account for the lung microbiome or detect changes in microbial diversity associated with disease. As a clinically applicable CF microbiome surveillance scheme, total sputum nucleic acids isolated by a standard high-throughput robotic method for accredited viral diagnosis were profiled for bacterial diversity using ribosomal intergenic spacer analysis (RISA) PCR. Conventional culture and RISA were performed on 200 paired sputum samples from 93 CF adults; pyrosequencing of the 16S rRNA gene was applied to 59 patients to systematically determine bacterial diversity. Compared to the microbiology data, RISA profiles clustered into two groups: the emerging nonfermenting Gram-negative organisms (eNFGN) and Pseudomonas groups. Patients who were culture positive for Burkholderia, Achromobacter, Stenotrophomonas, and Ralstonia clustered within the eNFGN group. Pseudomonas group RISA profiles were associated with Pseudomonas aeruginosa culture-positive patients. Sequence analysis confirmed the abundance of eNFGN genera and Pseudomonas within these respective groups. Low bacterial diversity was associated with severe lung disease (P < 0.001) and the presence of Burkholderia (P < 0.001). An absence of Streptococcus (P < 0.05) occurred in individuals with lung function in the lowest quartile. In summary, nucleic acids isolated from CF sputum can serve as a single template for both molecular virology and bacteriology, with a RISA PCR rapidly detecting the presence of dominant eNFGN pathogens or P. aeruginosa missed by culture (11% of cases). We provide guidance for how this straightforward CF microbiota profiling scheme may be adopted by clinical laboratories.

Long-term non-invasive ventilation in cystic fibrosis — Experience over two decades ☆

BACKGROUND Non-invasive ventilation (NIV) is accepted as a bridge to lung transplantation in cystic fibrosis (CF) but there is little evidence to support its use outside this setting. METHODS We reviewed the records of all patients with CF who received domiciliary NIV at our centre between 1991 and 2010. RESULTS Of 47 patients studied, 36% underwent lung transplantation, 28% died without transplantation and 30% remain alive on NIV. Median duration of NIV was 16 months (range 2-90). Mean FEV(1) fell by 212 ml over the year before NIV but increased by 18 ml in the following year (p<0.01). Individual response to NIV was associated with lower baseline and more rapid decline in FEV(1). From 1991 to 2000, 70% underwent lung transplantation; from 2001 to 2010 only 27% were transplanted. CONCLUSIONS NIV may slow or reverse the decline in lung function in advanced CF. NIV is increasingly used beyond a bridge to transplantation at our centre.

Reassessment of the importance of mucins in determining sputum properties in cystic fibrosis.

Background There is conflicting evidence about the importance of airway mucins (MUC5AC and MUC5B) in determining physical properties of sputum in cystic fibrosis (CF). We studied the effects of endogenous degradation of mucins on CF sputum elasticity and apparent mucin concentrations. Methods Elastic shear moduli (G′) and mucin concentrations in sputum of 12 CF patients were measured before and after incubation at 37 °C for 60 min. Results G′ fell from a median of 5.98 to 4.70 Pa (p = 0.01). There were significant falls in MUC5AC (8.2 to 5.2 μg/ml, p = 0.02) and MUC5B (17.3 to 12.5 μg/ml, p = 0.02) over the same period, and associated decrease in molecular weight and size. Conclusions Sputum is not inert and degradation reduces apparent mucin concentrations and sputum elasticity. Even if care is taken to process samples rapidly, sputum may therefore differ from secretions retained in airways. Previous studies may have underestimated the role of mucins in CF sputum.

Chronic Rhinovirus Infection in an Adult with Cystic Fibrosis

ABSTRACT Rhinovirus is a common cause of exacerbations of cystic fibrosis (CF) and is usually considered a self-limiting infection. We report a case of chronic infection with rhinovirus A type 33 in a 43-year-old male with CF which has persisted for over 2 years.

A therapeutic conundrum: recurrent cystic-fibrosis-related haemoptysis complicated by acute pulmonary embolism

The authors present the case of an older patient with cystic fibrosis (CF) and recurrent haemoptysis complicated by acute pulmonary embolism. The patient was treated successfully with a combination of anticoagulation and bronchial artery embolisation. The management of CF-related haemoptysis, the impact of an ageing CF population and the incidence of thromboembolic disease in CF are discussed.

Progressive unilateral lung collapse in cystic fibrosis-a therapeutic challenge:

Progressive collapse and destruction of an entire lung is an uncommon but recognized manifestation of cystic fibrosis (CF).1 This devastating complication presents a considerable challenge to both the CF multi-disciplinary team and the transplant surgeon. The evidence base to guide management of this condition is sparse, and in our clinical experience it has proved impossible to reverse the underlying process. Case reports of surgical intervention for complete lung collapse have demonstrated a high incidence of adverse outcomes.1–3 We report, in detail, the case of one patient with progressive unilateral lung collapse followed by a summary of a seven comparable cases encountered at our unit.

WS19.6 Changes in the weather and the respiratory health of adults with cystic fibrosis

Objectives: Fungi, particularly Aspergillus and Candida species, are increasingly found in cystic fibrosis (CF) airway fluids. However, their relationship to other CF pathogens, medications and lung function, especially in CF children, remains poorly understood. To address this question, we analyzed the associations of fungal colonization with microbiological and clinical parameters of pediatric CF patients. Methods: Fungal colonization was categorized in n = 128 CF patients based on Chotirmall et al. (Chest 2010). Candida albicans (CA) was the most prevalent fungus detected in CF airway fluids, followed by C. non-albicans > Aspergillus fumigatus (AF) > A. non-fumigatus species. Colonization with CA correlated positively with age, inhaled antibiotic use, and Aspergillus species, while an inverse correlation with Haemophilus and no association with S. aureus or Pseudomonas was found. Colonization with AF correlated positively with age, inhaled antibiotics, Pseudomonas, Stenotrophomonas, atypical mycobacteria and CF-related diabetes and inversely with Haemophilus. ABPA showed no correlation with AF colonization, but with non-fumigatus species and use of azithromycin. Colonization with AF or CA correlated inversely with cross-sectional FEV1, but not with MEF25. Colonization with AF correlated with longitudinal FEV1 decline. Conclusion: This study suggests that colonization with CA or AF is affected by bacterial co-colonization and may modulate lung function already in pediatric CF.

S45 Clinical efficacy of seasonal influenza vaccination in adults with cystic fibrosis

Introduction Influenza vaccination produces an adequate serological response in adults with cystic fibrosis (CF)1 and is a recommended part of routine CF care. There is little evidence to date, however, of a clinical benefit from influenza vaccination in this patient group. We compared prospectively the rate of influenza infection with vaccination status among 100 adults with CF over the 2010/2011 UK influenza season. Methods 100 adults with CF were enrolled in a prospective observational study of respiratory viruses between December 2010 and March 2011. Sputum, nose- and throat-swabs for PCR-based virological analysis were sent every 2 months and additionally at onset of acute respiratory illness through to June 2011. Prior to enrolment, sputum was sent for virology at onset of pulmonary exacerbations as part of routine care. Details of influenza vaccination status were obtained from the CF centres database and GP records. Previous infection with influenza A/H1N1 was determined from clinical records. Results Patients had a median age of 28 years (range 18–62). 88% had received the 2010/2011 seasonal influenza vaccine (A/California/7/2009/H1N1, A/Perth/16/2009/H3N2 & B/Brisbane/60/2008). 44% of the cohort had received the 2009 monovalent swine-origin influenza A/H1N1 vaccine and 8 patients had previously had PCR-confirmed swine-origin influenza. Over the study period there were 10 cases of influenza: 5 influenza A/H1N1, 4 influenza B and 1 dual influenza A/B infection. Among patients who received the 2010/2011 seasonal vaccine, 9/88 (10.2%) suffered influenza compared with 1/12 (8.3%) of those who had not been vaccinated (OR 1.25; 95% CI 0.14 to 10.9). All 9/9 patients who developed influenza despite being vaccinated were homozygous for the F508del mutation compared with 43/79 (55.7%) of vaccinated patients who did not develop influenza (p=0.009). No significant difference was seen between these groups with regard to age, gender, BMI, lung function, diabetes mellitus or use of oral corticosteroids. Conclusions Influenza vaccination may have limited clinical efficacy in adults with CF. The influence of CF genotype on susceptibility to influenza infection and response to vaccination requires further investigation.

124 Ribosomal RNA intergenic spacer analysis (RISA) as a rapid and diagnostic means to profile microbial diversity in cystic fibrosis sputum

123 A shotgun metaproteomics approach to study the faecal microbiome of patients with cystic fibrosis reveals a reduction of butyrate-producing bacteria G. Debyser1, B. Mesuere2, L. Clement2, G. Duytschaever1, P. Van Hecke1, P. Dawyndt2, K. De Boeck3, P. Vandamme1, B. Devreese1. 1Ghent University, Department of Biochemistry and Microbiology, Ghent, Belgium; 2Ghent University, Department of Applied Mathematics and Computer Science, Ghent, Belgium; 3University Hospital of Leuven, Department of Pediatrics, Leuven, Belgium