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We present the case of a patient with cystic fibrosis on long-term oral linezolid treatment for Mycobacteria abscessus lung infection who developed severe linezolid-induced lactic acidosis (LILA) resulting in deranged clotting and pancytopenia. The lactic acidosis was resistant to treatment with intravenous fluid but resolved within 20 hours of initiating continuous veno-venous haemofiltration. An unintended consequence of haemofiltration was that vascular access interfered with effective chest physiotherapy, resulting in worsened lung consolidation requiring prolonged intravenous antibiotic therapy for coexisting Pseudomonas aeruginosa infection. Given the potential mortality and morbidity of LILA, monitoring lactate levels may be clinically important but the optimum timing of monitoring is currently unclear., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: 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., Results: 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 <50%., Conclusions: This study provides a conservative estimate of excess inhaled medicines supply cost among adults with CF in the UK. The excess supply cost was highest among those with lowest EDC adherence, highlighting the importance of adherence support and supplying medicine according to actual use. MPR provides information about medicine supply but over-estimates actual medicine use., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: In CF, people with higher FEV 1 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. %FEV 1 , 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 FEV 1 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 %FEV 1 were independent predictors for IV recommendation by clinicians. Higher number of symptoms and lower %FEV 1 were also independent predictors for IV acceptance by adults with CF., Conclusions: Lower IV use among adults with higher %FEV 1 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa status influences cystic fibrosis (CF) clinical management but no 'gold standard' definition exists. The Leeds criteria are commonly used but may lack sensitivity for chronic P. aeruginosa. We compared clinicians' decision with the Leeds criteria in three adult CF centres. Two independent prospective datasets (Sheffield dataset, n = 185 adults; ACtiF pilot dataset, n = 62 adults from two different centres) were analysed. Clinicians involved in deciding P. aeruginosa status were blinded to the study objectives. Clinicians considered more adults with CF to have chronic P. aeruginosa infection compared to the Leeds criteria. This was more so for the Sheffield dataset (106/185, 57.3% with clinicians' decision vs. 80/185, 43.2% with the Leeds criteria; kappa coefficient between these two methods 0.72) compared to the ACtiF pilot dataset (34/62, 54.8% with clinicians' decision vs. 30/62, 48.4% with the Leeds criteria; kappa coefficient between these two methods 0.82). However, clinicians across different centres were relatively consistent once age and severity of lung disease, as indicated by the type of respiratory samples provided, were taken into account. Agreement in P. aeruginosa status was similar for both datasets among adults who predominantly provided sputum samples (kappa coefficient 0.78) or adults > 25 years old (kappa coefficient 0.82). Across three different centres, clinicians did not always agree with the Leeds criteria and tended to consider the Leeds criteria to lack sensitivity. Where disagreement occurred, clinicians tended to diagnose chronic P. aeruginosa infection because other relevant information was considered. These results suggest that a better definition for chronic P. aeruginosa might be developed by using consensus methods to move beyond a definition wholly dependent on standard microbiological results.

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF.

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: 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.

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 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.

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.

In patients with cystic fibrosis (CF), nasal intermittent positive pressure ventilation (NIPPV) is currently used as a short-term bridge to transplantation but its precise role has yet to be determined. Patients were offered a therapeutic trial of NIPPV when candidates for lung transplantation, with respiratory failure unresponsive to medical treatment. Twelve patients, six male of mean age of 26 +/- 1.4 years, had a trial of NIPPV. At recruitment the mean percentage predicted forced expired volume in one second (FEV1) was 15.1% +/- 1.2%, arterial carbon dioxide (PaCO2) 8.7 +/- 0.6 kPa, arterial oxygen (PaO2) with variable FiO2 7.4 +/- 0.6 kPa and arterial bicarbonate (HCO3-) 40.1 +/- 1.6 mmol l-1. Ten cases tolerated NIPPV for 1-15 months, mean 5.1 +/- 1.4 months, with subjective improvement in headache and quality of sleep. At 3 months, there was significant improvement in forced vital capacity, PaCO2 and arterial HCO3- and there was a reduction in the number of hospital inpatient days (P < 0.05). Subsequently three cases had lung transplantation, four died on the active list and three are awaiting organs. Two patients failed to tolerate NIPPV owing to abdominal bloating and increasing hypercapnia. In conclusion, NIPPV, if tolerated, was a useful adjunct in the treatment of CF patients with hypercapnic respiratory failure awaiting transplantation. Further prospective studies are required to determine the optimum time to commence NIPPV and to clarify its precise role.

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.

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.

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.