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Cystic fibrosis (CF) is a complex genetic, multiorgan disease. The CF Foundation (CFF) recommends a multidisciplinary team (physician, nurse, respiratory therapist, dietitian, physical therapist, social worker, mental health coordinator, clinic coordinator, and pharmacist) to work with patients and families. The objective of our study was to describe the impact of a pharmacist involved in the care of patients and families from their perspective. The CF Patient and Family Experience of Care (PFEC) is a voluntary, 50-question telephonic or internet-based survey designed to continuously collect information from patients and their families regarding their care experience. From August of 2017 through February of 2018, five questions were added to the internet survey to assess the impact of the pharmacist on the care experience. From the 666 respondents, 54% reported that a pharmacist was involved in their CF care. At two CF clinics designated as "full access" to a pharmacist, respondents reported a higher percentage of the CF-team discussed medications compared to those from three clinics designated as "limited access" to the pharmacist (95% vs 67%). Respondents in clinics with "full access" to a pharmacist were significantly more likely to get their medications refilled on time (78% vs 63%) and reported using fewer pharmacies to fill their medications. Pharmacist involvement in CF care may improve patient's access to medication and the ability to sustain use.

BackgroundAzithromycin treatment improves clinical parameters in patients with CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile of cells from patients receiving azithromycin is unknown.MethodsGene expression in association with macrophage polarization, inflammation, and tissue remodeling was assessed from sputum samples collected from patients with CF. Transcriptional profiles and clinical characteristics, including azithromycin therapy, were compared.ResultsExpression of NOS2 and TNFα was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with M1- (MMP9, NOS2, and TLR4) or M2-polarization (CCL18, fibronectin, and MR1) in select subject groups. These expression signatures did not significantly correlate with clinical characteristics.ConclusionsPro-inflammatory gene expression was low in subjects receiving AZM. Genes were stratified into groupings characteristic of M1- or M2-polarization, suggesting that overall polarization status is distinct among patient groups.

Intervention for cystic fibrosis lung disease early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstruction. Denufosol is a novel ion channel regulator designed to correct the ion transport defect and increase the overall mucociliary clearance in cystic fibrosis lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype.To evaluate the efficacy and safety of denufosol in patients with cystic fibrosis who had normal to mildly impaired lung function characteristic of early cystic fibrosis.A total of 352 patients greater than or equal to 5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24-week trial.Main outcome measures included change in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No significant differences between groups were observed for secondary endpoints including exacerbation rate and other measures of lung function. Denufosol was well tolerated with adverse event and growth profiles similar to placebo.Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279).

Background The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF). Objectives and Hypothesis To describe the baseline characteristics of the cohort and evaluate associations between potential risk factors and nutritional and respiratory characteristics at enrollment. We hypothesized that distinct demographic and environmental risk factors could be identified for poorer nutritional status and lung function at enrollment. Methods During 2004–2006, 1,700 children with CF were enrolled at 59 US CF centers. Children ≤12 years were eligible if they had no prior Pa infection (Pa-Never) or, if prior isolation of Pa from respiratory cultures, at least a 2-year history of Pa negative cultures (Pa-Past). Results One thousand one hundred seventeen participants (65.7%) were Pa-Never and 583 (34.3%) Pa-Past. Pa-never patients had a lower proportion of CFTR genotypes with both mutations in functional classes I, II, or III), higher lung function and less respiratory symptoms. Diagnosis after newborn or prenatal screening was associated with significantly higher mean weight, height, and FEV1 at enrollment, while maternal smoking during pregnancy appeared to worsen these parameters. Conclusions Children in this cohort with a remote history of Pa infection had a higher proportion of CFTR genotypes associated with severely reduced CFTR function as well as lower lung function and more respiratory symptoms than those without prior Pa infection. These observed differences in respiratory indices may reflect the impact of prior Pa airway infection and/or of CFTR genotype or other genetic factors predisposing both to earlier Pa acquisition and more severe lung disease. Key characteristics associated with nutritional and pulmonary status at enrollment included diagnosis after prenatal or neonatal screening (protective) and in utero cigarette exposure (harmful). Pediatr. Pulmonol. 2010; 45:934–944. © 2010 Wiley-Liss, Inc.

Background and Purpose. This investigation identified ventilation distribution, gas mixing, lung function, and arterial blood oxyhemoglobin saturation (Spo2) physiologic responses to 2 independent airway clearance treatments, high-frequency chest wall oscillation (HFCWO) and low positive expiratory pressure (PEP) breathing, for subjects who had cystic fibrosis (CF) and who were hospitalized during acute and subacute phases of a pulmonary exacerbation. Subjects. Fifteen subjects with moderate to severe CF were included in this study. Methods. Subjects performed single-breath inert gas tests and spirometry before and immediately after HFCWO and PEP breathing at admission and discharge. Arterial blood oxyhemoglobin saturation was monitored throughout each treatment. Results. At admission and discharge, PEP breathing increased Spo2 during treatment, whereas HFCWO decreased Spo2 during treatment. Ventilation distribution, gas mixing, and lung function improved after HFCWO or PEP breathing. Discussion and Conclusion. High-frequency chest wall oscillation and PEP breathing are similarly efficacious in improving ventilation distribution, gas mixing, and pulmonary function in hospitalized people with CF. Because Spo2 decreases during HFCWO, people who have moderate to severe CF and who use HFCWO should have Spo2 monitored during an acute exacerbation.

Study Objectives. To compare the susceptibility of respiratory cultures of Pseudomonas aeruginosa obtained from patients with cystic fibrosis to cefepime versus ceftazidime. The pattern of cumulative resistance of P. aeruginosa to cefepime in patients who had received at least one treatment course of cefepime between two sputum cultures was also characterized. Design. Prospective consecutive data collection. Setting. University-affiliated cystic fibrosis clinic and medical center. Patients. Eighty patients with cystic fibrosis who had at least one sputum culture positive for P. aeruginosa with reported microbiologic susceptibilities to cefepime and ceftazidime. Intervention. Patient data was collected and analyzed. Measurements and Main Results. Two hundred and thirty-one P. aeruginosa isolates were collected over 6 months. A total of 16.4% and 8.7% of the isolates were nonsusceptible to cefepime and ceftazidime, respectively (p=0.01). In eight patients who had not received cefepime before the study period, nonsusceptibility was 11.8% and 27.2% before and after exposure to cefepime, respectively. Conclusions. Susceptibility of P. aeruginosa isolates in patients with cystic fibrosis was lower with cefepime than with ceftazidime. Follow-up surveillance to determine changes in susceptibility of P. aeruginosa isolates to cefepime is warranted.

Intravenous continuous infusion of betalactam (CIBL) antibiotic and high dose extended interval (HDEI) aminoglycoside therapy theoretically maximize bacterial killing in treatment of Pseudomonas aeruginosa (PsA) in pulmonary exacerbations of cystic fibrosis (CF). We present the case of a 3-month-old female infant with CF who failed outpatient eradication of PsA with subsequent eradication using intravenous CIBL antibiotic and HDEI aminoglycoside therapy. This antibiotic combination should be considered in order to optimize pharmacodynamics for PsA eradication in CF patients before development of chronic colonization. Pediatr Pulmonol. 2008; 43:511–513. © 2008 Wiley-Liss, Inc.

Background. Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. Objective. This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. Methods. One hundred thirty patients (ages 5 to 17 years) were randomized to receive either iv ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or iv ceftazidime 50 mg/kg every 8 h plus iv tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. Results. All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. Conclusion. Sequential iv/oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

A two-year longitudinal study of thirty-five children used data gathered from pulmonary function tests, clinical measurements and standardized tests of depression, self-esteem and family environment to illustrate homeostatic interactions among biological and psychosocial adaptation to cystic fibrosis. Despite physical deterioration over the course of the study, children with cystic fibrosis reported lower depression and higher self-esteem than population norms, and improvements in psychological functioning. Decline in biological indicators of health was associated with increases on an index based on Family Environmental Scales (FES), subscales of cohesion, expressiveness and organization, and maintenance of high self-esteem and low depression. Presence of additional major life stressors was associated with deterioration in pulmonary function, higher levels of depression and poorer scores on the FES. These findings suggest that homeostatic interactions between children's health status and family functioning may moderate the physical and psychological sequelae of cystic fibrosis.

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI).Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms.Methods. Patients (n=31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared.Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp.,P<.0001for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE.Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF).To describe the baseline characteristics of the cohort and evaluate associations between potential risk factors and nutritional and respiratory characteristics at enrollment. We hypothesized that distinct demographic and environmental risk factors could be identified for poorer nutritional status and lung function at enrollment.During 2004-2006, 1,700 children with CF were enrolled at 59 US CF centers. Childrenor=12 years were eligible if they had no prior Pa infection (Pa-Never) or, if prior isolation of Pa from respiratory cultures, at least a 2-year history of Pa negative cultures (Pa-Past).One thousand one hundred seventeen participants (65.7%) were Pa-Never and 583 (34.3%) Pa-Past. Pa-never patients had a lower proportion of CFTR genotypes with both mutations in functional classes I, II, or III), higher lung function and less respiratory symptoms. Diagnosis after newborn or prenatal screening was associated with significantly higher mean weight, height, and FEV(1) at enrollment, while maternal smoking during pregnancy appeared to worsen these parameters.Children in this cohort with a remote history of Pa infection had a higher proportion of CFTR genotypes associated with severely reduced CFTR function as well as lower lung function and more respiratory symptoms than those without prior Pa infection. These observed differences in respiratory indices may reflect the impact of prior Pa airway infection and/or of CFTR genotype or other genetic factors predisposing both to earlier Pa acquisition and more severe lung disease. Key characteristics associated with nutritional and pulmonary status at enrollment included diagnosis after prenatal or neonatal screening (protective) and in utero cigarette exposure (harmful).

Möbius syndrome is a complex neurologic disorder characterized by congenital bilateral facial paralysis associated with lateral gaze paralysis. The syndrome has variable manifestations and several variants, some with somatic stigmata. In 1990, Möbius syndrome is conceptualized as a spectrum of clinical caudal brain-stem signs. Some deficits are manifested by laryngeal paralysis and aspiration. Sleep-disordered breathing syndromes have not been previously reported in association with Möbius syndrome. We report two children with Möbius syndrome and sleep-disordered breathing. Based on known pathologic findings and clinical manifestations, we believe that sleep-disordered breathing may be a common complication of Möbius syndrome and should be sought, since potential outcomes of such complications include serious morbidity. ( J Child Neurol 1991;6:73-77).

This investigation identified ventilation distribution, gas mixing, lung function, and arterial blood oxyhemoglobin saturation (SpO2) physiologic responses to 2 independent airway clearance treatments, high-frequency chest wall oscillation (HFCWO) and low positive expiratory pressure (PEP) breathing, for subjects who had cystic fibrosis (CF) and who were hospitalized during acute and subacute phases of a pulmonary exacerbation.Fifteen subjects with moderate to severe CF were included in this study.Subjects performed single-breath inert gas tests and spirometry before and immediately after HFCWO and PEP breathing at admission and discharge. Arterial blood oxyhemoglobin saturation was monitored throughout each treatment.At admission and discharge, PEP breathing increased SpO2 during treatment, whereas HFCWO decreased SpO2 during treatment. Ventilation distribution, gas mixing, and lung function improved after HFCWO or PEP breathing.High-frequency chest wall oscillation and PEP breathing are similarly efficacious in improving ventilation distribution, gas mixing, and pulmonary function in hospitalized people with CF. Because SpO2 decreases during HFCWO, people who have moderate to severe CF and who use HFCWO should have SpO2 monitored during an acute exacerbation.

Although pulmonary function tests are used to evaluate acute changes in obstructive airway disease in patients with cystic fibrosis (CF), these tests are relatively difficult to perform in young children or severely ill patients and may be costly. Other standard tests (eg, the Shwachman-Kulczycki and National Institutes of Health [NIH] scoring systems) evaluate disease severity and predict prognosis but do not measure day-to-day changes in clinical status. They thus provide little information for assessing the start of acute pulmonary exacerbation. Alternative scoring systems are needed to better identify the start of pulmonary exacerbation, to predict worsening or improvement of respiratory function after intervention, and to distinguish the scores from illness severity scores. This study was undertaken to compare a new 10-component, 50-point-maximum, acute clinical scoring system with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) variables in children with CF who were experiencing an acute pulmonary exacerbation before antimicrobial therapy was initiated and until the end of therapy. One hundred thirty children aged 5 to 17 years (median age, 11 years) had a median NIH score of approximately 64 (range, 39 to 85) at admission. The cystic fibrosis clinical score (CFCS) at admission was found to correlate highly with the modified NIH score at study entry (r = -.68, P = 0.0001 ). The total CFCS at entry was correlated inversely with both FEV1 (r = -.57, P = 0.0001) and FVC (r = -.55, P = 0.0001) measurements; crackles, dyspnea, sputum production, and respiratory rate were the 4 components most highly associated with either pulmonary function variable. The change in total CFCS from start to end of antimicrobial therapy also correlated with changes in FEV1 (r = -.31, P = 0.0016) and change in FVC (r = -.47, P = 0.0001). Clinical improvement was observed in all patients at the end of therapy, and only 1 patient had an increase in total CFCS. Patients who experienced clinical relapse had a mean increase of 8.5 points in the CFCS from end of therapy to 2- to 4-week follow-up, indicating worsening signs and symptoms of acute exacerbation. These data suggest that the CFCS is a predictive and optional surrogate of pulmonary function in assessing the health of patients with CF. Following further validation, this scoring system could be used to evaluate health status in the outpatient setting, the need for hospitalization, and subsequent improvement during an acute pulmonary exacerbation, as well as to compare the efficacy of therapeutic regimens.

Congenital lobar emphysema (CLE) is an important cause of infantile respiratory distress that may require surgical intervention. We retrospectively reviewed the clinical and imaging findings in eight infants with CLE. In our series, CLE was more common in females, predominantly involved the right lung, often presented with an opaque lobe from retained fetal lung fluid, and frequently involved the lower lobes, multiple segments or lobes, and both lungs. Most patients with CLE were diagnosed and managed on the basis of clinical and plain radiographic findings alone. Computed tomography, and occasionally ventilation/perfusion scintigraphy, were helpful in confirming the diagnosis and in guiding management decisions in several cases; bronchoscopy showed that stenosis of the right mainstem bronchus was the cause of CLE in one case. Three patients experienced progressive worsening of respiratory distress and required surgical resection of the affected lobe for cure; the remaining five patients were managed medically with eventual remission of symptoms.

The onset of cor pulmonale is a common terminal finding in patients with cystic fibrosis. Since Doppler echocardiography can detect changes in diastolic filling patterns prior to the onset of either systolic dysfunction or clinical symptoms, we utilized this technique to determine whether detectable changes in left ventricular diastolic filling patterns exist in patients with cystic fibrosis. Among 25 patients, the proportion of left ventricular filling attributable to atrial contraction was significantly increased when compared with age-matched control individuals. When filling patterns were compared with severity of pulmonary disease, worsening pulmonary disease was directly correlated to shifts in left ventricular filling patterns. We conclude that changes in left ventricular patterns of relaxation are detectable early in the course of cystic fibrosis and that such changes are probably progressive. Early detection could lead to therapeutic trials designed to improve left ventricular filling and delay the onset of overt cor pulmonale. (Chest 1991; 99:646–50)

Auscultation of the infant chest reveals lung sounds that seem different from those of adults. To characterize this subjective difference, we compared the phonopneumographic median frequencies of lung sounds of seven full-term and six premature infants with those of seven adults free of cardiopulmonary disease. The median frequencies over the upper lobes for the adults, term infants, and premature infants were 282 +/- 63(SD) Hz, 383 +/- 80 Hz, and 483 +/- 86 Hz, respectively. At this location the differences among the three groups were significant (p less than 0.01). Over the lower lobes, the median frequencies for the adults, term infants, and premature infants were 243 +/- 56 Hz, 386 +/- 76 Hz, and 390 +/- 63 Hz, respectively. Here the difference between the adults and both groups of infants was significant (p less than 0.01), but that between the term and premature infants was not. We conclude that the normal lung sounds of newborn infants contain higher-frequency components than those of adults. We postulate that this difference is the result of less filtering of the lung sound in infants. This difference should be considered when lung sounds of infants are described or assessed for the presence of abnormalities.

Summary. The purpose of this experiment was to test the hypothesis that airway closure impedes the production of lung sounds at low lung volume. We recorded breath sounds in three healthy men during inspiratory vital capacity manoeuvres in upright, head-down and lateral decubitus postures. We then compared the rate of increase of breath sound intensity (BSI) between the dependent and non-dependent lung zones. Closing volumes, measured separately, were normal in the upright but increased in the head-down postures. The data revealed no consistent lag in the rate of increase of BSI over the dependent lung zones in any of the postures. Our data suggest that airway closure does not influence lung sound generation. If true, this implies that lung sounds are produced proximally to the site of physiologic airway closure.