Airway Disease in Children with Primary Ciliary Dyskinesia: Impact of Ciliary Ultrastructure Defect and Genotype.

Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, progressive airway damage, and obstructive lung disease. Although the association of ciliary ultrastructure defect/genotype with the severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated. We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD.

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear.

Methods: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation.

Impact of azithromycin on serum inflammatory markers in children with cystic fibrosis and new Pseudomonas.

Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population.

Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial.

The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. PROMISE is a postapproval study to understand the broad effects of ETI through 30 months' clinical use in a more diverse U.S.

Morbidity and Mortality in the Obese Trauma Intensive Care Unit Patient.

Introduction: Obesity is an epidemic in the United States, known to be associated with comorbidities. However, some data show that obesity may be a protective factor in some instances. The purpose of this study is to determine if there are differences in morbidity and mortality when comparing the obese and non-obese critically ill trauma patient populations.

PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy.

Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older.

Comparison of Multiple Breath Washout and Spirometry in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis and Healthy Controls.

In cystic fibrosis (CF), the lung clearance index (LCI), derived from multiple breath washout (MBW), is more sensitive in detecting early lung disease than FEV; MBW has been less thoroughly evaluated in young patients with primary ciliary dyskinesia (PCD). Our objectives were ) to evaluate the sensitivity of MBW and spirometry for the detection of mild lung disease in young children with PCD and CF compared with healthy control (HC) subjects and ) to compare patterns of airway obstruction between disease populations. We used a multicenter, single-visit, observational study in children with PCD and CF with a forced expiratory volume in 1 second (FEV) greater than 60% predicted and HC subjects, ages 3-12 years.

Virtual navigation tested on a mobile app is predictive of real-world wayfinding navigation performance.

Virtual reality environments presented on tablets and smartphones have potential to aid the early diagnosis of conditions such as Alzheimer's dementia by quantifying impairments in navigation performance. However, it is unclear whether performance on mobile devices can predict navigation errors in the real world. We compared the performance of 49 participants (25 females, 18-35 years old) at wayfinding and path integration tasks designed in our mobile app 'Sea Hero Quest' with their performance at similar tasks in a real-world environment.

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

Rationale: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood.

Objectives: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype.

Methods: This was a prospective, longitudinal (5 yr), multicenter, observational study.

Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD).

Target Audience: Clinicians investigating adult and pediatric patients for possible PCD.

Methods: Systematic reviews and, when appropriate, meta-analyses were conducted to summarize all available evidence pertinent to our clinical questions.

Preschool Multiple-Breath Washout Testing. An Official American Thoracic Society Technical Statement.

Background: Obstructive airway disease is nonuniformly distributed throughout the bronchial tree, although the extent to which this occurs can vary among conditions. The multiple-breath washout (MBW) test offers important insights into pediatric lung disease, not available through spirometry or resistance measurements. The European Respiratory Society/American Thoracic Society inert gas washout consensus statement led to the emergence of validated commercial equipment for the age group 6 years and above; specific recommendations for preschool children were beyond the scope of the document.

Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis.

Rationale: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation.

Objectives: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF.

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection.

Objective: Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF.

Methods: Two populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs.

Barriers and Facilitators to Scientific Writing Among Applied Epidemiologists.

Context: Communication in the form of written and oral reports and presentations is a core competency for epidemiologists at governmental public health agencies. Many applied epidemiologists do not publish peer-reviewed articles, limiting the scientific literature of best practices in evidence-based public health.

Objectives: To describe the writing and publishing experiences of applied epidemiologists and identify barriers and facilitators to publishing.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations.

Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents.

Assessment and Detection of Early Lung Disease in Cystic Fibrosis.

It is now widely accepted that cystic fibrosis (CF) lung disease begins in infancy and early childhood, with evidence of structural, functional, and inflammatory changes present even in asymptomatic children. This realization, coupled with broad adoption of CF newborn screening in the United States, Canada, Europe, and Australia, has raised the possibility for primary prevention of CF lung disease. To intervene before respiratory symptoms develop in infants and preschool children with CF, sensitive testing modalities are necessary to define and follow mild CF lung disease, both for research and for clinical purposes.