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Abstract: Background: Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Purpose: Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. Study design: A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12months. The primary endpoint is change in FEV1 (L) from baseline to 12months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. Conclusions: This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. [Copyright &y& Elsevier]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy. OBJECTIVE: To determine the efficacy of thalidomide in suppressing cough in patients with IPF. DESIGN: 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028) SETTING: 1 university center. PARTICIPANTS: 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods. MEASUREMENTS: The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life. RESULTS: CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide. LIMITATION: This was a single-center study of short duration and small sample size focused on symptom-specific quality of life. CONCLUSION: Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results. PRIMARY FUNDING SOURCE: Celgene Corporation. [ABSTRACT FROM AUTHOR]

RATIONALE: The prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV(1) decline in CF is unknown. OBJECTIVES: To determine the association between MRSA respiratory infection and FEV(1) decline in children and adults with CF. METHODS: This was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996-2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV(1) decline, adjusted for confounders, in individuals aged 8-21 years and adults (aged 22-45 yr). Two different statistical models were used to assess robustness of results. MEASUREMENTS AND MAIN RESULTS: The study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (> or =3 MRSA cultures; average, 6.8 positive cultures) and were subsequently followed for an average of 3.5 years. Even after adjustment for confounders, rate of FEV(1) decline in individuals aged 8-21 years with persistent MRSA was more rapid in both statistical models. Their average FEV(1) decline of 2.06% predicted/year was 43% more rapid than the 1.44% predicted/year in those without MRSA (difference, -0.62% predicted/yr; 95% confidence interval, -0.70 to -0.54; P < 0.001). Effect of MRSA on FEV(1) decline in adults was not clinically significant. CONCLUSIONS: Persistent infection with MRSA in individuals with CF between the ages of 8 and 21 years is associated with a more rapid rate of decline in lung function. [ABSTRACT FROM AUTHOR]

Rationale: Treatment guidelines for vitamin D monitoring and supplementation in cystic fibrosis (CF) have recently been developed and published by a consensus committee, but have not been prospectively tested.Objectives: To use these guidelines to determine the percentage of adults with CF requiring vitamin D repletion therapy and to evaluate the effectiveness of the currently recommended high-dose oral ergocalciferol repletion protocol.Methods: Prospective study of clinical outcomes after therapy with the recommended vitamin D repletion algorithm.Results: Of 134 adults with CF, 109 (81.3%) were found to have 25-hydroxyvitamin D (25-OHD) levels below the recommended 30 ng/ml. Sixty-six of these adults completed the recommended course of 400,000 IU of oral ergocalciferol over 2 months, and only five (8%) responded with correction of their serum 25-OHD to the goal of 30 ng/ml or greater (mean change, +0.3 ng/ml; from 18.8 to 19.1 ng/ml). In the 33 adults with CF who also completed the recommended second course of 800,000 IU of ergocalciferol over 2 months, none demonstrated correction of their deficiency (mean change, -1.2 ng/ml).Conclusion: The results of this study demonstrate that a majority of adults with CF have serum 25-OHD levels below 30 ng/ml, and the currently recommended ergocalciferol repletion regimen often does not fully correct vitamin D deficiency and may need to be revised to include even higher dosing of ergocalciferol. Further work is needed to establish the ideal 25-OHD level for maximizing calcium absorption and bone health in CF. [ABSTRACT FROM AUTHOR]

Study Objectives: To determine whether distraction therapy with nature sights and sounds during flexible bronchoscopy (FB) reduces pain and anxiety.Design: Randomized controlled trial.Setting: Teaching hospital in Baltimore, MD.Patients: Consecutive adult patients (n = 80) undergoing FB with conscious sedation.Intervention: Nature scene murals were placed at the bedside, and patients were provided a tape of nature sounds to listen to before, during, and after the procedure. Patients assigned to the control group were not offered either the nature scene or the sounds.Measurements and Results: The primary outcomes were patient ratings of pain control (a 5-point scale ranging from poor to excellent) and anxiety. In a multivariate ordinal logistic regression model, the odds of better pain control were greater in the intervention patients than in the control patients (odds ratio [OR], 4.76; 95% confidence interval [CI], 1.35 to 16.7), after adjustment for age, gender, race, education, health status, and dose of narcotic medication. Older patients and patients with better health status reported significantly less pain. There was no difference in patient-reported anxiety between the two groups (OR, 0.87; 95% CI, 0.39 to 1.96).Conclusions: Distraction therapy with nature sights and sounds significantly reduces pain in patients undergoing FB. Although the precise mechanism of this beneficial effect requires further investigation, clinicians should consider this nonintrusive strategy in addition to standard analgesic medications in patients undergoing painful, invasive procedures. [ABSTRACT FROM AUTHOR]

Background: Sweat chloride concentration is used both for CF diagnosis and for tracking CFTR modulator efficacy over time, but the relationship between sweat chloride and lung health is heterogeneous and informed by CFTR genotype. Here, we endeavored to characterize ion transport in eccrine sweat glands (ESGs)., Methods: First, ESGs were microdissected from a non-CF skin donor to analyze individual glands. We established primary cultures of ESG cells via conditional reprogramming for functional testing of ion transport by short circuit current measurement and examined cell composition by single-cell RNA-sequencing (scRNA-seq) comparing with whole dissociated ESGs. Secondly, we cultured nasal epithelial (NE) cells and ESGs from two people with CF (pwCF) to assess modulator efficacy. Finally, NEs and ESGs were grown from one person with the CFTR genotype F312del/F508del to explore genotype-phenotype heterogeneity., Results: ESG primary cells from individuals without CF demonstrated robust ENaC and CFTR function. scRNA-seq demonstrated both secretory and ductal ESG markers in cultured ESG cells. In both NEs and ESGs from pwCF homozygous for F508del, minimal baseline CFTR function was observed, and treatment with CFTR modulators significantly enhanced function. Notably, NEs from an individual bearing F312del/F508del exhibited significant baseline CFTR function, whereas ESGs from the same person displayed minimal CFTR function, consistent with observed phenotype., Conclusions: This study has established a novel primary culture technique for ESGs that allows for functional ion transport measurement to assess modulator efficacy and evaluate genotype-phenoytpe heterogeneity. To our knowledge, this is the first reported application of conditional reprogramming and scRNA-seq of microdissected ESGs., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)