Exercise as airway clearance therapy (ExACT) in cystic fibrosis: a UK-based e-Delphi survey of patients, caregivers and health professionals.

Replacing traditional airway clearance therapy (tACT) with exercise (ExACT) in people with cystic fibrosis (pwCF) is a top research priority. A UK-based e-Delphi consensus was performed to inform the type(s), duration and intensity of ExACT. The expert panel comprised CF physiotherapists, doctors, pwCF and parents/partners. Exercise ACT was considered to be aerobic activity, of at least 20 min duration and intense enough to elicit deep breathing. Consensus was reached that assessment breaths, coughs and huffs should accompany exercise to remove loose secretions, with support for trials to investigate ExACT versus tACT during times of stable disease but not pulmonary exacerbations.

Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study.

BACKGROUND: Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity. METHODS: A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without. RESULTS: 12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03). CONCLUSIONS: These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF.

Deaths in childhood from cystic fibrosis: 10-year analysis from two London specialist centres.

INTRODUCTION: Death in childhood from cystic fibrosis (CF) is now an uncommon event in the U.K. We wished to assess the circumstances surrounding deaths (and lung transplantation) in the modern era of CF care. METHODS: A retrospective review was carried out pooling data from two large paediatric specialist CF units in London for the 10-year period 2000-2009 inclusive. RESULTS: There were 11 deaths and eight children who had a lung transplant out of 1022 children cared for in this period. Median age of death was 14.2 years and transplant 13.0 years, with a female preponderance (82% deaths and 75% transplants). Apart from one child (forced expiratory volume in 1 s (FEV1) 69%), lung function indicated severe lung disease (median FEV1 33%, range 12%-69%). Values 5 years prior to death were not predictive (median FEV1 62%, range 32%-96%), and those 1 year prior were similar to the last recorded levels. Almost all (10/11) died in hospital and 5/11 (45%) were ventilated. Respiratory failure was the commonest mode of death (64%). Only four children (36%) were receiving palliative care, and in six cases (55%) care was withdrawn. CONCLUSIONS: The number of deaths in children with CF was small but often unpredictable, so active management was continued until late in the majority, reflected by the fact that almost all were in hospital, and more than half were ventilated. If death from respiratory failure is anticipated following a steady decline, palliative care should be instituted well in advance, with attention to appropriate end of life care.

Effects of a supervised, outpatient exercise and physiotherapy programme in children with cystic fibrosis.

Previous work suggests benefit from outpatient exercise and physiotherapy in children with cystic fibrosis (CF), namely improved exercise capacity and lung function measures, as well reduced intravenous (IV) antibiotic needs. Our study aim was to investigate the effect of a year-long supervised outpatient exercise and physiotherapy programme in children with CF. Subjects with CF aged ≥10 years who had received ≥4 courses of IV antibiotics in 2009 were enrolled and seen fortnightly for supervised exercise and physiotherapy throughout 2010. In addition, they were expected to exercise three times weekly, and if unwell complete additional physiotherapy sessions extra to usual chest physiotherapy. Assessments of exercise capacity using the Modified Shuttle Test (MST) and quality of life (QOL; CFQ-UK) were recorded at baseline and after 1 year. Regular spirometry was performed before and throughout the study. Data were collected on IV antibiotic days. 12 subjects (6 female) were enrolled with mean (95% CI) age of 13.3 (11.8-14.6) years at study entry. A significant reduction in IV antibiotic days from 60 (56-64) days in 2009 to 50 (44-56) in 2010 (P = 0.02) was noted, along with improved MST distance (m) [735 (603-867) vs. 943 (725-1,161), P = 0.04] and level attained [9.4 (8.4-10.5) vs. 11.1 (9.6-12.6), P = 0.04]. Significant improvements in CFQ-UK scores for physical [59 (47-72) vs. 83 (74-92), P = 0.001], emotional [63 (55-72) vs. 84 (74-93), P < 0.001], treatment [41 (30-51) vs. 61 (48-73), P = 0.002], and respiratory [54 (42-66) vs. 76 (70-82), P = 0.002] domains were noted. The mean (95% CI) rate of change of FEV(1) was -4 (-18, +10)% in 2009, but was +6 (-2, +13)% in 2010, although this did not reach statistical significance. Supervised, outpatient exercise and physiotherapy are associated with improvements in QOL and exercise tolerance, a reduction in IV antibiotic days, and a trend towards reducing lung function decline in children with CF. The cost of IV antibiotics was reduced by £66,384 ($104,000) in 2010 when compared with 2009. Such cost-benefit may have implications for workforce planning and service provision.

Blurring the lines in interferon {gamma} receptor deficiency: an infant with near-fatal airway disease.

Deficiencies of the interferon γ (IFN-γ) pathway have become a well-recognized cause of nontuberculous mycobacterial infection. We report here a case of autosomal dominant IFN-γ receptor 1 (IFN-γ-R1) deficiency presenting at the unusually young age of 16 months with a severe clinical course. Mycobacterium avium complex was cultured from bronchial washings of a child who presented with primary endobronchial disease after a 4-month history of rhinorrhea, wheeze, and acute lobar consolidation. A maternal history of multifocal Mycobacterium kansasii osteomyelitis and cutaneous M avium complex led to genetic confirmation of IFN-γ-R1 818del4 deletion (a 4 base pair deletion at nucleotide position 818) in both family members. This case demonstrates the link between mycobacterial disease and IFN-γ pathway deficiency, the diagnosis of which facilitates more accurate therapy and genetic counseling. The case also raises questions about the reported distinct presentation, treatment, and prognosis of autosomal dominant and recessive IFN-γ-R1 phenotypes.

Fungal pleural effusion secondary to a rare cause of pancreatic pseudocyst.

We report a case of fungal pleural effusion secondary to presumed valproate induced pancreatitis with pseudocyst and stricture formation. A child with dyskinetic cerebral palsy who had been on sodium valproate for several years was transferred for drainage of a left sided pleural effusion. Pleural fluid culture consistently grew Candida glabrata although the patient was treated with broad-spectrum antibiotic and antifungal therapy. Clinical deterioration ensued with abdominal discomfort, feed intolerance, and re-accumulation of the effusion. Investigations revealed a large pancreatic pseudocyst compressing the stomach and impairing pancreatic function. Subsequent therapeutic evacuation of pancreatic fluid demonstrated C. glabrata. This case underscores that pleural disease may be secondary to abdominal pathology, and always to consider rare side-effects of medication in the face of a puzzling clinical picture.

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis.

INTRODUCTION: Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. MATERIALS AND METHODS: DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. RESULTS: 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean +/- SEM rates of change of %predicted FEV(1)/year (0.9 +/- 2.3 (DD) vs. - 3.9 +/- 2.8 (DG), p = 0.22), %predicted FEV(1) (76 +/- 8 vs. 74 +/- 11), p = 0.91), or z scores for height ( - 0.47 +/- 0.26 vs. - 0.24 +/- 0.19, p = 0.48) and weight ( - 0.01 +/- 0.22 vs. - 0.29 +/- 0.27, p = 0.44). Median +/- SE survival age at first PA isolation was also not significantly different (3.5 +/- 2.1 vs. 6.5 +/- 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. CONCLUSIONS: Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.