The effect of the weather on pulmonary exacerbations and viral infections among adults with cystic fibrosis.

The effect of changes in the weather on the respiratory health of patients with cystic fibrosis (CF) is unclear. We conducted a prospective study to determine the impact of climate and season on the incidence of viral respiratory infections (VRI) and pulmonary exacerbations (PEx) among adults with CF. Between December 2010 and April 2012, 98 adults with CF were followed for 12 months. Polymerase chain reaction assays for nine viruses were performed on sputum, nose and throat swabs every 2 months and additionally at onset of PEx. Hourly temperature and relative humidity measurements were recorded throughout the study. Statistical analysis utilized generalized estimating equation (GEE) models. Pre-specified criteria for VRI and PEx were met at 29% and 37% of visits, respectively. Rhinovirus accounted for 72% of identified viruses. Incidence of rhinovirus peaked in autumn while non-rhinovirus VRI peaked in winter. Rhinovirus was associated with increased mean temperatures (OR 1.07; p = 0.001), while non-rhinovirus VRI was associated with lower mean temperatures (OR 0.87; p < 0.001). PEx occurred frequently throughout the study with no clear seasonal pattern observed. There was no significant association between climate variables and the incidence of either PEx or antibiotic prescription. There is a seasonal pattern to VRI in adults with CF. The incidence of VRI but not PEx is associated with changes in ambient temperature.

Successful treatment of cepacia syndrome with combination nebulised and intravenous antibiotic therapy.

We report the case of successful treatment of a 31-year-old lady with cystic fibrosis and an en-bloc liver-pancreas transplant, who developed cepacia syndrome on a background of chronic infection with the ET12 epidemic strain of Burkholderia cenocepacia. Combination therapy with nebulised and intravenous meropenem and tobramycin led to clinical improvement with a return to baseline function and complete resolution of the acute chest X-ray changes.

A novel solution for severe urinary incontinence in women with cystic fibrosis.

BACKGROUND: To explore whether Tension-free Vaginal Tape offers a solution for women with cystic fibrosis who suffer from severe stress incontinence. METHODS: Four adults with cystic fibrosis were formally assessed by gynaecological and urological specialists, prior to hospital admission for surgery. RESULTS: The procedure was tolerated well by all patients. In three, leakage ceased completely. The fourth patient experienced considerable improvement in symptoms. CONCLUSIONS: Tension-free Vaginal Tape is a safe, effective and worthwhile solution for stress incontinence in females with cystic fibrosis.

The changing epidemiology of Burkholderia species infection at an adult cystic fibrosis centre.

BACKGROUND: This study reviews the impact of changing infection control practices at the Manchester Adult Cystic Fibrosis Centre (MACFC) upon the epidemiology of Burkholderia species infections. METHODS: We reviewed strain and genomovar typing of all available Burkholderia isolates at our centre between 1983-2006. RESULTS: The incidence/prevalence of infection with Burkholderia species between 1983-1990 was below 5%/9% each year. There was a rise in incidence/prevalence of Burkholderia species between 1991 and 1994 with a peak of 16.3%/31.2% in 1992. Following complete cohort segregation, the incidence has fallen to below 3% for all but one year and the prevalence has gradually reduced to 9.3% in 2005. Currently, there is an increase in the prevalence to 10.6% for the first time since 1994, predominantly due to patients with unique infections transferring into the unit from referring centres. The presence of unique strains now exceeds transmissible strains for the first time since 1991. CONCLUSIONS: Infection control measures including patient segregation have controlled spread of transmissible B. cenocepacia strains, but not the acquisition of unique strains. Unique strains of Burkholderia species now account for the majority of new infections at the Manchester Adult Cystic Fibrosis Centre.

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care.

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.

Deficient nifedipine oxidation: a rare inherited trait associated with cystic fibrosis kindreds.

Previous studies have indicated that there is weak genetic linkage between the defective gene in cystic fibrosis (CFTR) and the gene encoding the nifedipine metabolizing enzyme P4503A4 which are both located on chromosome 7. To examine further this possible association, nifedipine metabolism was investigated in a group of 59 volunteers, and 17 adult cystic fibrosis patients and 37 of their relatives. In agreement with the majority of previous studies, the volunteer group showed a unimodal distribution of recoveries for the major metabolite M-II ranging from 33 to 78% excretion in 8 h. In the case of both the cystic fibrosis patients and their parents, the distribution of recoveries was shifted to the left with five out of 20 parents and three out of 11 unrelated cystic fibrosis patients showing recoveries below the range observed in the volunteer group. This poor metabolism appeared to be both reproducible and heritable and did not appear to be a consequence of mutations in the CFTR gene.

Long-term change in exercise capacity, body mass, and pulmonary function in adults with cystic fibrosis.

STUDY OBJECTIVES: Cross-sectional studies in patients with cystic fibrosis (CF) have shown that exercise capacity is correlated with pulmonary function and body mass. We have examined whether the same relationships are seen longitudinally in adults with CF. DESIGN: Subjects who first performed progressive maximal cycle ergometry between 1986 and 1989 were retested using an identical protocol a mean of 6.3 years later. PARTICIPANTS AND SETTING: Adults with CF attending a regional center. MEASUREMENTS AND RESULTS: The principal exercise measures were peak oxygen uptake (VO2peak), ventilation (VEpeak), oxygen saturation, and heart rate. Spirometry, weight, and height were also recorded at each time point. At baseline, subjects had a mean age of 19.8 years, body mass index (BMI) of 19.0, FEV1 of 69% predicted, VO2peak of 1.56 L/min, and VEpeak of 48.9 L/min. At repeated testing after a mean interval of 6.3 years, the FEV1 had fallen significantly to 54% predicted (p < 0.001) and the BMI had risen significantly to a mean of 20.9 (p < 0.001). There were no significant differences in VO2peak or VEpeak, although VEpeak was a significantly higher proportion (72% vs 61%) of predicted maximal voluntary ventilation. CONCLUSIONS: Adults with mild to moderate pulmonary dysfunction were able to increase body mass and maintain VO2peak despite a declining FEV1. VO2peak was not reduced by the decrease in FEV1 because VEpeak was unaffected. Improved nutrition may have contributed to maintaining fitness.

Bone histomorphometry in adult patients with cystic fibrosis.

STUDY OBJECTIVE: Low bone mineral density is a common complication of cystic fibrosis (CF), and recent studies have implicated vitamin D insufficiency as a significant etiologic factor. The aim of this study was to establish whether there was bone biopsy evidence of vitamin D deficiency osteomalacia in patients with CF and to document the general histomorphometric characteristics of CF bone. PATIENTS AND METHODS: A retrospective descriptive and histomorphometric study of postmortem L2/L3 vertebral bone biopsy specimens was undertaken on tissue from 11 posttransplant CF patients and 4 nontransplanted CF patients. Control data were derived from postmortem bone specimens from 15 young adults. RESULTS: Bone from all CF patients was characterized by severe osteopenia in both trabecular and cortical bone. At the cellular level, there was decreased osteoblastic and increased osteoclastic activity. The reduction in osteoblastic activity was due to both a decrease in osteoblast number and a decrease in the biosynthetic potential of osteoblasts. The osteoclastic changes were due to an increase in the number of osteoclasts. The increase in osteoclasis and the uncoupling of osteoblastic and osteoclastic activity resulted in an increase in resorptive surfaces. Although there were few significant differences between the transplanted and nontransplanted CF groups, both cortical and trabecular bone mass tended to be lower after transplantation. None of the CF undecalcified biopsy specimens showed osteoid parameters characteristic of vitamin D deficiency osteomalacia. CONCLUSIONS: CF patients have an unusual and complex pattern of cellular changes within bone that are not typical of vitamin D deficiency osteomalacia.

Splenomegaly and splenectomy in sarcoidosis.

The natural history of 30 patients with sarcoidosis who showed histological evidence of granulomatous involvement of the spleen has been studied; 24 patients had splenomegaly, 16 of whom had splenectomy. The main indication for splenectomy was splenomegaly and resultant discomfort. Corticosteroids reduced spleen size but reduction or withdrawal of the relatively high dosage required resulted in rebound splenomegaly within a period of three months to three years. Haematological abnormalities were controlled by splenectomy in all patients so affected, but the natural history of their sarcoidosis remained unaltered.