A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens. METHODS: A literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis. RESULTS: Twenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing. CONCLUSION: The findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.

Respiratory muscle training for cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of most recent search: 11 June 2020. A hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases. Date of most recent search: 05 October 2020. SELECTION CRITERIA: Randomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Review authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system. MAIN RESULTS: Authors identified 20 studies, of which 10 studies with 238 participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the 10 included studies were published as abstracts only and lacked concise details, thus limiting the information available. Eight studies were parallel studies and two of a cross-over design. Respiratory muscle training interventions varied dramatically, with frequency, intensity and duration ranging from thrice weekly to twice daily, 20% to 80% of maximal effort, and 10 to 30 minutes, respectively. Participant numbers ranged from 11 to 39 participants in the included studies; five studies were in adults only, one in children only and four in a combination of children and adults. No differences between treatment and control were reported in the primary outcome of pulmonary function (forced expiratory volume in one second and forced vital capacity) or postural stability (very low-quality evidence). Although no change was reported in exercise capacity as assessed by the maximum rate of oxygen use and distance completed in a six minute walk test, a 10% improvement in exercise duration was found when working at 60% of maximal effort in one study (n = 20) (very low-quality evidence). In a further study (n = 18), when working at 80% of maximal effort, health-related quality of life improved in the mastery and emotion domains (very low-quality evidence). With regards to the review's secondary outcomes, one study (n = 11) found a change in intramural pressure, functional residual capacity and maximal inspiratory pressure following training (very low-quality evidence). Another study (n=36) reported improvements in maximal inspiratory pressure following training (P < 0.001) (very low-quality evidence). A further study (n = 22) reported that respiratory muscle endurance was longer in the training group (P < 0.01). No studies reported significant differences on any other secondary outcomes. Meta-analyses could not be performed due to a lack of consistency and insufficient detail in reported outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence to suggest whether this intervention is beneficial or not. Healthcare practitioners should consider the use of respiratory muscle training on a case-by-case basis. Further research of reputable methodological quality is needed to determine the effectiveness of respiratory muscle training in people with cystic fibrosis. Researchers should consider the following clinical outcomes in future studies; respiratory muscle function, pulmonary function, exercise capacity, hospital admissions, and health-related quality of life. Sensory-perceptual changes, such as respiratory effort sensation (e.g. rating of perceived breathlessness) and peripheral effort sensation (e.g. rating of perceived exertion) may also help to elucidate mechanisms underpinning the effectiveness of respiratory muscle training.