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Background\ud \ud Studies in separate cohorts suggest possible discrepancies between inhaled medicines supplied (median 50-60%) and medicines used (median 30-40%). We performed the first study that directly compares CF medicine supply against use to identify the cost of excess medicines supply.\ud \ud \ud \ud Methods\ud \ud This cross-sectional study included participants from 12 UK adult centres with ≥1 year of continuous adherence data from data-logging nebulisers. Medicine supply was measured as medication possession ratio (MPR) for a 1-year period from the first suitable supply date. Medicine use was measured as electronic data capture (EDC) adherence over the same period. The cost of excess medicines was calculated as whole excess box(es) supplied after accounting for the discrepancy between EDC adherence and MPR with 20% contingency.\ud \ud \ud \ud Results\ud \ud Among 275 participants, 133 (48.4%) were females and mean age was 30 years (95% CI 29-31 years). Median EDC adherence was 57% (IQR 23-86%), median MPR was 74% (IQR 46-96%) and the discrepancy between measures was median 14% (IQR 2-29%). Even with 20% contingency, mean potential cost of excess medicines was £1,124 (95% CI £855-1,394), ranging from £183 (95% CI £29-338) for EDC adherence ≥80% to £2,017 (95% CI £1,507-2,526) for EDC adherence

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug. We describe a case of transaminitis developing nine months after the initiation of Kaftrio, which progressed to liver necrosis despite stopping Kaftrio and took many months to resolve. The patient had experienced significant improvement in lung function and overall health while on Kaftrio and deteriorated when it was stopped. He was keen to restart; however, Kaftrio was not reinstated due to the potential risk of acute liver failure.

Rationale and aims\ud \ud Lung health of people with cystic fibrosis (PwCF) can be preserved by daily use of inhaled therapy. Adherence to inhaled therapy, therefore, provides an important process measure to understand the success of care and can be used as a quality indicator. Defining adherence is problematic, however, since the number of prescribed treatments varies considerably between PwCF. The problem is less pronounced among those with Pseudomonas aeruginosa (PA), for whom at least three daily doses of nebulized therapy should be prescribed and who thus constitute a more homogeneous group. The UK CF Registry provides routine data on PA status, but data are only available 12 months after collection. In this study, we aim to prospectively identify contemporary PA status from historic registry data.\ud \ud \ud Method\ud \ud UK CF Registry data from 2011 to 2015 for PwCF aged ≥16 was used to determine a pragmatic prediction rule for identifying contemporary PA status using historic registry data. Accuracy of three different prediction rules was assessed using the positive predictive value (PPV). The number and proportion of adults predicted to have PA infection were determined overall and per center for the selected prediction rule. Known characteristics linked to PA status were explored to ensure the robustness of the prediction rule.\ud \ud \ud Results\ud \ud Having CF Registry defined chronic PA status in the two previous years is the selected definition to predict a patient will have PA infection within the current year (population-level PPV = 96%-97%, centre level PPV = 85%-100%). This approach provides a subset of data between 1852 and 1872 patients overall and a range of 8 to 279 patients per center.\ud \ud \ud Conclusion\ud \ud Historic registry data can be used to contemporaneously identify a subgroup of patients with chronic PA. Since this patient group has a narrower treatment schedule, this can facilitate a better benchmarking of adherence across centers.

Introduction In CF, people with higher FEV1 are less aggressively treated with intravenous (IV) antibiotics, with resultant negative impact on their health outcomes. This could be entirely clinician-driven, but patient choice may also influence IV use. In this prospective observational study, we explored IV recommendations by clinicians and IV acceptance by adults with CF to understand how clinical presentations consistent with exacerbations resulted in IV use. Methods Clinical presentations consistent with exacerbations, IV recommendation by clinicians and IV acceptance by patients were prospectively identified for every adult with CF in Sheffield throughout 2016, excluding those who had lung transplantation (n = 7) or on ivacaftor (n = 13). Relevant demographic data, e.g. %FEV1, were extracted from medical records. Multi-level mixed-effects logistic regression models were used to compare IV recommendations vs non-recommendations for all clinical encounters, and IV acceptance vs non-acceptance for all IV recommendations. Results Among 186 adults (median age 27 years, median FEV1 78.5%), there were 434 exacerbation events and 318 IV use episodes following 1010 clinical encounters. Only 254 (58.5%) of exacerbations were IV treated. A diagnosis of exacerbation, higher number of symptoms and lower %FEV1 were independent predictors for IV recommendation by clinicians. Higher number of symptoms and lower %FEV1 were also independent predictors for IV acceptance by adults with CF. Conclusions Lower IV use among adults with higher %FEV1 was influenced by both clinicians' and patients’ decisions. Using IV antibiotics as an exacerbation surrogate could under-estimate exacerbation rates and conceal differential treatment decisions according to varying clinical characteristics.

This European Respiratory Society/Thoracic Society of Australia and New Zealand statement outlines a review of the literature and expert opinion concerning the management of reproduction and pregnancy in women with airways diseases: asthma, cystic fibrosis (CF) and non-CF bronchiectasis. Many women with these diseases are now living into reproductive age, with some developing moderate-to-severe impairment of lung function in early adulthood. The statement covers aspects of fertility, management during pregnancy, effects of drugs, issues during delivery and the post-partum period, and patients’ views about family planning, pregnancy and parenthood. The statement summarises current knowledge and proposes topics for future research, but does not make specific clinical recommendations.

BackgroundReducing nebulisation times for tobramycin solution for inhalation in cystic fibrosis (CF) may improve compliance.MethodsIn this single-dose, open-label, two-way crossover study, 13 subjects (7 CF, 6 healthy) were randomised to receive tobramycin via eFlow rapid or LC Plus jet nebuliser. Drug deposition in the lung using gamma scintigraphic imaging, nebulisation times, pharmacokinetics, and safety were evaluated.ResultsIn CF patients, whole-lung deposition was 40% less with the eFlow rapid compared with LC Plus nebulisers was (8.9±0.8%, and 15.1±6.0%, p>0.05). Nebulisation time was shorter with eFlow rapid compared to LC Plus (7.0min versus 20.0min, p

Cystic Fibrosis (CF) is the most common life-shortening recessive genetic disease in the UK. Far from being a condition managed exclusively by paediatricians with sufferers dying in early childhood, CF is now a condition in which adults outnumber children with the condition, and the death of a child in a paediatric centre is rare. As increasing numbers of young people grow up relatively healthy it is unsurprising they begin to ask about relationships, sex, fertility and the possibility of having a child. This paper briefly describes the genetics, pathophysiology and clinical features of CF with an emphasis on how it pertains to female reproduction. The management of women with CF considering having a baby including contraception, preparation for pregnancy, the pregnancy itself, delivery and the post natal period will be discussed. Contraindications to pregnancy, method of termination, and pregnancy after transplantation will also be considered. Much of the detailed management is given in the European Guidelines for the Management of Pregnancy in Women with CF on which this paper is based.

Progressive pulmonary disease may preclude the option of pregnancy for a number of women in their child-bearing years due to the severity of the disease. For a subset of women with chronic lung disease including cystic fibrosis, pregnancy is possible, but can have a devastating effect both on the prospective mother and fetus. The potential hazards of pregnancy in cystic fibrosis or other progressive pulmonary diseases may trigger a moral conflict between physician and patient. The female patient may argue that her autonomy cannot be circumscribed and that the physician is obliged to assist her reproductive efforts. The physician can counter that his/her participation in potentially harmful interventions is not consistent with professional norms requiring adherence to the principles of beneficence and nonmaleficence. Whenever possible, the ethical conflict between physician and patient should be resolved before initiation of pregnancy. We propose that this best be done through structured negotiations between physician and patient with the goal of constructing an ethical framework for reducing the moral tension between the two. Steps in the negotiating process include defining the therapeutic alliance, information exchange, dialog, and deliberation. As part of the information exchange, it is important to discuss alternatives to pregnancy such as adoption and surrogacy, especially when there are strong contraindications to pregnancy. If negotiations reach a satisfactory conclusion for both sides, there should be a well-delineated consensual agreement to commence the pregnancy with the full support of the medical team.

Background Evidence shows lack of competency among health care professionals (HCPs) to demonstrate correct inhaler technique to patients. Aim: We conducted a multicentre RCT at 2 tertiary hospitals to investigate whether simulation-based training using Aerosol Inhalation Monitor (AIM) and written information is more effective compared to training using written information alone. Method 160 HCPS (69 doctors, 80 nurses, 8 physiotherapists, 3 pharmacists) were randomised into 2 groups of simulation and written information (Intensive Intervention Arm (IIA; n=80)) and written information only (Minimal Intervention Arm (MIA; n=80)) arms. Inhaler technique was assessed using the AIM machine and checklist score (maximum score 20; 10 for MDI and 10 DPI) which were conducted immediate-post teaching and 1-week after. Results: Cumulative combined (MDI+DPI) median scores for the IIA group showed significant improvement at post-teaching compared to MIA at 1-week (p

Background: Emerging resistance of Pseudomonas aeruginosa within cystic fibrosis (CF) populations is attributed to antibiotic pressure and spread of transmissible strains. We describe increasing resistance of P. aeruginosa isolates, resulting in the identification of two multiresistant strains and their impact on morbidity. Methods: Susceptibility reports of all P. aeruginosa isolates since 1998 in our unit were reviewed. Isolates were submitted for genomic finger-printing by pulsed-field gel electrophoresis. Clinical measures and the consumption of treatment resources were compared between those harbouring resistant organisms and those with sensitive strains. Results: Analysis of 407 reports from 43 patients revealed isolation of multiresistant (MR) organisms increased during 1999. Those harbouring MR strains consumed more resources than non-MR. Strain typing showed a new ‘Sheffield' strain in seven patients (100% MR), and the ‘Liverpool' strain in 10 patients (40% MR). Individuals in these groups consumed significantly more resources than 23 patients with unique, susceptible strains (4% MR). Discussion: Increasing resistance in isolates of P. aeruginosa may herald the arrival of a transmissible strain in CF Units which though sometimes sensitive, may become multiply resistant and require more intensive treatment. We now segregate those with transmissible strains from each other and from those with unique strains.

While it has long been appreciated that up to 98% of men with cystic fibrosis (CF) are infertile due to a failure to develop, or early blockage of, the mesonephric ducts and vas deferens,1 the effect of CF on the fertility of women is less clear. Survival is now into the fourth decade of life and, with the largest growth in the CF population seen in the adult age groups,2 it is not surprising that the issues of fertility and reproduction are increasingly raised in adult clinics. Pregnancy is possible and increasing numbers of children are born to women with CF each year.3 Since the first pregnancy in 1960,4 management of all aspects of CF has improved and so the prognosis for mother and child has also improved. This paper reviews the pathophysiology of CF in the female reproductive tract, its effect on fertility and the ability to carry a pregnancy, and the outcome for mother and infant. CF is an autosomal recessive disease arising from abnormalities on the long arm of chromosome 7. Defective production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein5—a complex channel regulating the passage of chloride and, indirectly, sodium and water across luminal cell membranes—results in thickened and desiccated secretions throughout the respiratory and alimentary tracts, sweat ducts, and the reproductive organs. The principal manifestations in adults are due to undernutrition resulting from pancreatic insufficiency and malabsorption, and respiratory failure due to chronic infection, bronchiectasis, and progressive lung destruction. Diabetes mellitus and cirrhosis are secondary manifestations resulting from pancreatic and biliary damage and are increasingly seen in older patients. CFTR is found in large quantities on the cervix6 and, although anatomically normal, histologically the columnar epithelium is distorted by mucus filled balloon or cygnet ring cells. The …

Summary The lungs of people with cystic fibrosis (CF) are affected by a basic ion transport defect leading to more viscid airway mucus. This is an ideal breeding ground for bacteria with which the lungs can become chronically colonised from an early age, leading to progressive obstructive pulmonary disease. The principles of treatment include airway clearance by physiotherapy and prophylaxis and treatment of infection with antibiotics. An audit of the physiotherapy service and knowledge and use of nebulisers by adults attending the Regional Cystic Fibrosis Centre at Birmingham Heartlands Hospital is presented. A self-administered questionnaire revealed that despite regular review and tuition by experienced senior CF physiotherapists, adherence, knowledge and practices were unsatisfactory. The need for individually tailored airway clearance techniques and exercise programmes was highlighted. Clinical guidelines covering in particular nebulised/inhaled drug usage and timing in relation to physiotherapy were shown to be necessary to augment practical teaching. Improved access to out-patient physiotherapy services and regular review when well at home were requested by many CF adults. Practical changes to the service have been implemented and recommendations made with a view to further assessment in 12 months to complete the audit loop.

BACKGROUND: There has been increasing concern since 1979 about the emergence of Pseudomonas cepacia (Burkholderia cepacia) in patients with cystic fibrosis in the UK and elsewhere. Colonisation of the sputum has been shown to be associated with increased morbidity and mortality. Evidence suggests person to person transmission and some centres have segregated those colonised with B cepacia from other patients with cystic fibrosis. The outcome of patients colonised by B cepacia has been studied, together with the effects of strict segregation. METHODS: The outcome in 18 patients with sputum colonised by B cepacia was compared with that in age, sex, and severity matched controls with no evidence of B cepacia colonisation by a retrospective case note study. RESULTS: No difference between cases or controls were found in the 24 month period prior to colonisation by B cepacia in lung function, number of days in hospital, or outpatient visits. Colonisation led to an increased rate of loss of lung function and utilisation of hospital services. There was an increase in the numbers of transplants and deaths amongst the cases. Since 1992 there have been only three new cases of B cepacia colonisation and the incidence and prevalence of the organism has fallen dramatically since segregation commenced. CONCLUSIONS: B cepacia appears to be linked to the decline in colonised individuals. There was no evidence that colonisation occurred in patients declining for other reasons. B cepacia colonisation confers a worse prognosis than Pseudomonas aeruginosa alone. Segregation appears to limit the spread of the organism from infected individuals to other patients with cystic fibrosis.

With significant improvements in longevity, women with cystic fibrosis are increasingly likely to consider pregnancy and parenthood. This article reviews the literature relating to medical and psychosocial research that informs the decision-making process these women undertake.

The case history is presented of a patient with acute respiratory failure complicated by nasal obstruction resulting in intolerance of nasal ventilation. Urgent insertion of nasal stents permitted restoration of ventilation with resolution of breathlessness and stabilisation of arterial blood gases.

Diabetes mellitus (DM) has been recognized as a complication of cystic fibrosis (CF) for almost 50 years and commonly develops around 20 years of age. The prevalence increases with age and, with improved survival of those with CF, approaches 30% in certain centres. Its development appears to have a significant impact on pulmonary function and may increase mortality by up to six-fold. Subjects with CF are rarely ketosis-prone and phenotypically lie between Type 1 and Type 2 DM. Microvascular complications are recognized, although paucity of data does not permit a clear description of their natural history. An annual oral glucose tolerance test from the age of 10 years is recommended for screening, but logistical difficulties have led some groups to develop specific algorithms to aid diagnosis. Insulin sensitivity in CF is much debated and may depend upon the degree of glucose intolerance. Insulin resistance occurs in the presence of infection, corticosteroid usage and hyperglycaemia, whilst hepatic insulin resistance is considered an adaptation to CF. There is no universal consensus on the treatment of hyperglycaemia. With increased longevity of individuals with CF, greater numbers will develop diabetes and the diabetes physician is destined to play a greater role in the multidisciplinary CF team.

The medical management of a patient with Crohn's disease should take into account the activity, site and behaviour of disease, and should be discussed with the patient, and 5-aminosalicylates are a group of medications which have been commonly used. Sulfasalazine is a combination of 5-aminosalicylic acid and sulfapyridine which acts only as a carrier to the colonic site of action but can still cause systemic side-effects1 including lung disease. In mesalazine the specific sulfapyridine-related side-effects, especially pulmonary reactions, are avoided. However, we present a case of lung fibrosis which was associated with mesalazine in a Crohn's patient.

Following an attempted suicide by drowning in a vat of mineral oil, a previously fit man survived the usually fatal lipoid pneumonia resulting from total immersion after intensive support and prolonged steroid therapy with recovery of chest radiography and pulmonary function at one year.

Outcomes for mother and baby have much improved The first successful pregnancy in a woman with cystic fibrosis was reported in 1960--at a time when the median survival of children with the disease was less than 10 years.1 The patient died six weeks after delivery, and the authors concluded that “cystic fibrosis is seriously complicated by pregnancy.” Since then reports have documented a gradual change from high fetal loss and maternal death due to cor pulmonale and respiratory failure to a good chance of a successful full term delivery of healthy infants to mothers whose overall health may be little changed.2 3 4 5 Sadly, this outcome is not available to patients whose health is poor or to those few women who have been sterilised or warned not to conceive. How, then, in the late 1990s should doctors approach the issues …

BACKGROUND--As women with cystic fibrosis are living longer, pregnancy is becoming increasingly common. The combined experience of pregnancies in women with cystic fibrosis from adult centres in the Midlands and North of England has been examined. METHODS--A retrospective study of the case notes of 22 pregnancies in 20 patients with cystic fibrosis examined changes in lung function, body weight, and microbiological status during the course of pregnancy. Duration of pregnancy, birth weight, and maternal survival were amongst other variables studied. The relation between values before pregnancy and important outcome measures were examined. RESULTS--Eighteen of 22 pregnancies were completed producing healthy, non-cystic fibrosis infants (12 female). Mothers lost 13% of FEV1 and 11% of FVC during pregnancy, most of which was regained. Body weight changes were variable, but most mothers gained weight (mean weight gain 5.7 kg). Microbiological status remained unchanged. Six infants were preterm and two were light for dates. Four mothers died up to 3.2 years following delivery. Of the prepregnancy parameters examined, %FEV1 showed the best correlation with maternal weight gain, gestation, birth weight, and maternal survival. CONCLUSIONS--Pregnancy was well tolerated by most mothers with cystic fibrosis although those with moderate to severe lung disease (%FEV1 < 60%) before pregnancy fared worse, producing preterm infants and suffering increased loss of lung function and mortality compared with mildly affected mothers. Prepregnancy %FEV1 appears to be the most useful predictor of important outcome measures in pregnancies in women with cystic fibrosis.

The use of a Heimlich flutter valve in an adult patient with cystic fibrosis with hypercapnic respiratory failure which allowed resolution of a persisting pneumothorax after failure of conventional tube drainage is reported. The patient was managed at home and avoided surgical pleurodesis which could have jeopardised transplantation at a later date.

Introduction The association between gastro-oesophageal reflux (GOR) and various respiratory disorders including cystic fibrosis (CF) is widely acknowledged. Although the exact nature of this relationship is uncertain, it is thought that reflux aspiration is a contributing factor in lung dysfunction in these patients. Patients with GOR typically report symptoms such as heartburn, regurgitation, and occasionally atypical symptoms such as cough. It has been hinted that GOR in CF patients may be “silent” making detection and treatment often difficult. We piloted a cross-sectional survey to gain a better understanding of the perception of GOR and its impact on lung function. Methods Consenting patients completed two validated questionnaires regarding GOR symptoms which were scored and ranked (Gastro-oesophageal Reflux Symptom Questionnaire and Reflux Symptom Index). Patients were stratified by score and divided into two pilot groups; SGOR (symptomatic-highest scores) and AGOR (asymptomatic-lowest scores). Both groups underwent 24-h multiple intraluminal impedance/pH metry (MII) and high-resolution manometry (HRM) for positioning of MII probe. MII studies were assessed for the number of GOR events, proximal reflux events (PREs), and total proximal bolus exposure (TPBE). Patients remained on all current medication including PPIs. Clinical data were collected and compared retrospectively including most recent lung function results (FEV1). Result 53/110 patients completed questionnaires and 10 from each group were invited to undergo investigation—11 were completed successfully (age 18–55 years; four male, seven female; seven SGOR, four AGOR). There was little difference in the mean number of events between the groups (range 16–75, mean—SGOR 38, AGOR 42; (normal on PPI=48, off PPI=73)). There was no correlation between symptom scores (SS) and number of GOR events but there was a moderate negative correlation between the number of GOR events/FEV1. There was no significant difference in the mean number of PREs between the groups (range 1–31; mean SGOR=11, AGOR=22). TPBE ranged from 0.2–342 s. No correlation was shown between; number of PREs/SS, number of PREs/FEV1 and TPBE/FEV1. Conclusion This small pilot study indicated that CF patients demonstrate impaired awareness of GOR and supports the theory that GOR is associated with poorer lung function. While there was no significant difference in the number of PREs between the groups, levels were higher in the AGOR group. This suggests that CF patients have poor perception of proximal reflux, which could increase the likelihood of aspiration. Based on these findings we aim to continue the survey to gain a more comprehensive assessment of the perception of GOR in adults with CF.

Objective To identify pregnancies in women with cystic fibrosis and describe obstetric, infant and maternal medical outcomes in relation to the severity of maternal disease. Design Retrospective study, based on casenotes. Setting Eleven cystic fibrosis centres in the United Kingdom. Population Pregnant women with cystic fibrosis. Methods Single observer medical and obstetric casenote review categorising maternal cystic fibrosis (e.g. genotype, pancreatic, hepatic and diabetic status) and pre-pregnant severity (e.g. weight and lung function) and noting fetal outcome and maternal morbidity. Main outcome measures Completed pregnancies and pregnancy losses, fetal outcome and complications, maternal morbidity, such as changes in weight, lung function, pulmonary infections during and after pregnancy. Relation of outcomes to severity of maternal cystic fibrosis. Results From 72 pregnancies identified, the outcomes were known for 69; there were 48 live births (70%) of which 22 were premature (46%); 14 therapeutic abortions (20%); and 7 miscarriages (10%). There were no stillbirths, neonatal or early maternal deaths. Three major fetal anomalies were seen, but no infant had cystic fibrosis. At the conclusion of our study three pregnancies were still continuing. Prematurity with increased fetal complications and maternal morbidity with infection, declining lung function and poor weight gain were associated with poor pre-partum lung function. Conclusion Pregnancy occurs in women with cystic fibrosis of all degrees of severity. Outcomes for the infant are generally good but are variable for the mother. Predicting outcome on the basis of maternal severity is difficult but lung function appears to be the most significant determining factor. Pregnancy may be normal in women with normal lung function (forced expiratory volume > 80%). However, it may adversely affect mild and moderate lung disease due to cystic fibrosis and should be avoided in pulmonary hypertension, cor pulmonale and when forced expiratory volume < 50% predicted. Ideally, all pregnancies should be planned with prior counselling and monitored by dedicated cystic fibrosis teams, including obstetricians who are experienced in managing high risk pregnancies.

Sarah Bache and Frank Edenborough uncover scores of health problems associated with making music