Although nontuberculous mycobacteria (NTM) are recognized pathogens in adolescent and adult patients with cystic fibrosis (CF), the role of NTM in younger CF patients is not well-defined. To explore NTM infection in CF patients less than 12 years old, a retrospective review was performed. Prevalence was estimated from routine mycobacterial cultures of bronchoalveolar lavage (BAL) specimens collected over a 3-year period. NTM-positive cultures were obtained from 9 of 258 BALs collected from 7 of 114 different patients (5 months to 11 years of age). Further data were acquired from microbiological and clinical records of all pediatric patients with CF over a 10-year period. A total of 17 patients had at least one positive mycobacterial culture at less than 12 years of age, 5 of whom had positive cultures before age 5. The most commonly identified organisms were Mycobacterium avium-complex and Mycobacterium abscessus. Of the 17 patients, 10 met American Thoracic Society (ATS) microbiological criteria for mycobacterial disease, and 7 did not. The two groups did not differ with respect to age, gender, or presence of other respiratory pathogens. Patients who met ATS microbiological criteria for disease were more likely to have positive smears for acid-fast bacilli and grow Mycobacterium abscessus from culture. These patients also had a greater decline in lung function over time than patients who did not meet the microbiologic criteria. These data suggest that NTM represent a clinically significant pathogen, even in young patients with cystic fibrosis.

Inflammation can be demonstrated in the airway mucosa of asthmatics, even in the absence of overt symptoms, but the pathogenesis of this chronic inflammation is incompletely defined. It has been suggested that inflammatory cytokines produced by epithelium may play important roles in this process. Therefore, we measured the cytokines interleukin-8 (IL-8), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in nasal lavage fluids from school-age children who were (1) "normal" (nonallergic/nonasthmatic), (2) allergic to house-dust mite antigen but nonasthmatic (no history of wheezing), or (3) allergic and asthmatic (history of > or = 10 wheezing episodes). Children underwent a single nasal lavage procedure while asymptomatic and on no anti-inflammatory medications or anti-histamines. In addition to cytokine concentrations, cell counts, differentials, albumin, histamine, and eosinophil cationic protein (ECP) concentrations were determined in nasal lavage fluids. Significant increases in IL-8 and ECP were observed in asthmatics compared with both normals and allergic nonasthmatics. Overall, IL-8 in nasal lavage fluids correlated significantly with ECP. Allergic nonasthmatics did not have significant increases in cytokines or other mediators compared with normal subjects. Concentrations of IL-6 did not differ significantly among the three groups, and GM-CSF was undetectable in all samples tested. We conclude that increased IL-8 production and eosinophil activation are characteristic of the airways of asthmatic children when asymptomatic, and we speculate that IL-8 plays a role in the maintenance of airway inflammation in asthma.

This review seeks to re-introduce cystic fibrosis (CF) clinicians to the pharmacology of drug-drug interactions among medications commonly used in CF and provide a framework for understanding these interactions among medications outside the scope of this discussion. We here focus on drugs impacted by the cytochrome P-450 (CYP450) enzyme system and on interactions involving antimicrobials, psychotropic medications, and cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Particular attention is needed when prescribing rifampin, azole antifungals and the CFTR modulators, ivacaftor, and lumacaftor/ivacaftor, in combination with other medications. The complexities of these interactions provide a strong rationale for case management by pharmacists and pharmacologists as a routine part of CF care. Pediatr Pulmonol. 2016;51:S61-S70. © 2016 Wiley Periodicals, Inc.

In clinically stable children with CF, systemic antibiotics result in greater short-term reduction in lower airways inflammation than inhaled antibiotics.

Gentamicin and standard-dose ibuprofen were administered to an adolescent with cystic fibrosis who developed renal failure and severe vestibulotoxicity. A contributing factor was possible suboptimal intravascular volume status. Because of the potential severity of this drug interaction, hydration status and renal and vestibular functions should be closely monitored in patients receiving ibuprofen and intravenous aminoglycosides concomitantly.