Nasal nitric oxide May not differentiate primary ciliary dyskinesia from certain primary immunodeficiencies.

The diagnosis of primary ciliary dyskinesia (PCD) is made through a combination of clinical features supported by a panel of diagnostic tests. Our cases highlight the similarities in the clinical presentation of patients with the specific immunodeficiency activated phosphatidylinositol 3-kinase delta syndrome 1 (or PIK3CD-related disorder) and PCD. We highlight the importance of repeating nasal nitric oxide testing when PCD has not been confirmed by genetic or ciliary electron micrograph analysis in the setting of an expanded suppurative lung disease differential that includes considerations for immunodeficiency as well as PCD.

Progress in Diagnosing Primary Ciliary Dyskinesia: The North American Perspective.

Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended. The purpose of this narrative review is to provide insight on the North American PCD diagnostic process, to enhance the understanding of and adherence to current guidelines, and to promote collaboration with diagnostic pathways used outside of North America.

The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study.

BACKGROUND: Ivacaftor has produced significant improvement in certain individuals with cystic fibrosis (CF), though the full metabolic effects of treatment remain unknown. Abnormalities in fatty acid metabolism have previously been shown to be a characteristic of CFTR dysfunction. We hypothesized that as a reflection of this clinical improvement, ivacaftor would improve plasma fatty acid levels and decrease urine prostaglandin E metabolite levels. METHODS: This study analyzed plasma fatty acid levels and urine prostaglandin E metabolites (PGE-M) in 40 subjects with CF participating in the G551D observational (GOAL) study who demonstrated response to the medication by a significant decrease in sweat Cl levels. Paired samples were analyzed before and after 6months of ivacaftor treatment. RESULTS: Linoleic acid and docosahexaenoic acid levels, which are typically low in individuals with CF, did not significantly increase with ivacaftor treatment. However, arachidonic acid levels did decrease with ivacaftor treatment and there was a significant decrease in the arachidonic acid metabolite PGE-M as measured in the urine [median: before treatment 17.03ng/mg Cr; after treatment 9.06ng/mg Cr; p<0.001]. Furthermore, there were fatty acid age differences observed, including pediatric participants having significantly greater linoleic acid levels at baseline. CONCLUSION: Ivacaftor reduces inflammatory PGE without fully correcting the plasma fatty acid abnormalities of CF. Age-related differences in fatty acid levels were observed, that may be a result of other clinical factors, such as diet, clinical care, or drug response.

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

BACKGROUND: Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). METHODS: This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. RESULTS: Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. CONCLUSIONS: Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation.

Pulmonary hypertension in the premature infant: a challenging comorbidity in a vulnerable population.

PURPOSE OF REVIEW: This review is written from the perspective of the pediatric clinician involved in the care of premature infants at risk for pulmonary hypertension. The main objective is to better inform the clinician in the diagnosis and treatment of pulmonary hypertension in premature infants by reviewing the available relevant literature and focusing on the areas for which there is the greatest need for continued research. RECENT FINDINGS: Continued knowledge regarding the epidemiology of pulmonary hypertension in the premature infant population has aided better diagnostic screening algorithms. Included in this knowledge, is the association of pulmonary hypertension in infants with bronchopulmonary dysplasia (BPD). However, it is also known that beyond BPD, low birth weight and other conditions that result in increased systemic inflammation are associated with pulmonary hypertension. This information has led to the recent recommendation that all infants with BPD should have an echocardiogram to evaluate for evidence of pulmonary hypertension prior to discharge from the neonatal ICU. SUMMARY: Pulmonary hypertension can be a significant comorbidity for premature infants. This review aims to focus the clinician on the available literature to improve recognition of the condition to allow for more timely interventions.