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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.
Subject(s)
Cystic Fibrosis , Reproduction , Adult , Australia , Cystic Fibrosis/therapy , Female , Fertility , Humans , New Zealand , PregnancyABSTRACT
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.
Subject(s)
Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Pseudomonas Infections/complications , Pseudomonas Infections/epidemiology , Adult , Cross-Sectional Studies , Female , Humans , Male , Multiple Chronic Conditions/epidemiology , Pseudomonas , Pseudomonas Infections/diagnosis , Pseudomonas Infections/microbiology , Sputum/microbiology , United Kingdom/epidemiology , Young AdultABSTRACT
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.
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RATIONALE AND AIMS: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
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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 (nâ¯=â¯7) or on ivacaftor (nâ¯=â¯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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cystic Fibrosis/drug therapy , Cystic Fibrosis/physiopathology , Administration, Intravenous , Adult , Anti-Bacterial Agents/therapeutic use , Cystic Fibrosis/epidemiology , Disease Progression , Female , Forced Expiratory Volume/drug effects , Humans , Male , Patient Outcome Assessment , Prospective Studies , Respiratory Function Tests/methodsSubject(s)
Cystic Fibrosis/drug therapy , Learning Health System , Medication Adherence , Adult , England , Female , Humans , Male , Nebulizers and Vaporizers , Retrospective StudiesABSTRACT
Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
Subject(s)
Communicable Diseases, Emerging/microbiology , Cystic Fibrosis/microbiology , Drug Resistance, Multiple, Bacterial , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Animals , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/pathology , Communicable Diseases, Emerging/transmission , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Genome, Bacterial , Genomics , Humans , Incidence , Lung/microbiology , Lung/pathology , Mice , Mice, SCID , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium Infections, Nontuberculous/transmission , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/isolation & purification , Phylogeny , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/transmission , Polymorphism, Single Nucleotide , Sequence Analysis, DNAABSTRACT
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-effects 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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Crohn Disease/drug therapy , Mesalamine/adverse effects , Pulmonary Fibrosis/chemically induced , Aged, 80 and over , Humans , Male , Pulmonary Fibrosis/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Reducing nebulisation times for tobramycin solution for inhalation in cystic fibrosis (CF) may improve compliance. METHODS: In 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. RESULTS: In 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<0.05). Lung deposition in healthy subjects was comparable between both devices. CONCLUSIONS: eFlow rapid reduces the nebulisation time of tobramycin and can potentially improved compliance in patients with CF.
Subject(s)
Cystic Fibrosis/drug therapy , Lung/diagnostic imaging , Nebulizers and Vaporizers , Tobramycin , Administration, Inhalation , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Biological Availability , Cystic Fibrosis/diagnostic imaging , Cystic Fibrosis/physiopathology , Dose-Response Relationship, Drug , Drug Delivery Systems , Drug Monitoring , Female , Humans , Male , Middle Aged , Organ Specificity/drug effects , Radionuclide Imaging , Respiratory Function Tests , Tobramycin/administration & dosage , Tobramycin/adverse effects , Tobramycin/pharmacokineticsABSTRACT
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.