A multi-disciplinary approach to chronic cough in children.

Objectives: (1) To highlight the important causes of chronic and recurrent cough in children. (2) To discuss multidisciplinary approach to management of chronic/recurrent pediatric cough. Methods: Review of scholarly articles, guidelines, expert panels via PubMed and Google Scholar. Conclusion: Chronic cough (CC) in children is mainly attributed to persistent bacterial bronchitis, asthma, nonspecific cough, and gastroesophageal reflux disease (GERD) symptoms. A multi-disciplinary approach is cost-effective and aids with earlier diagnosis and appropriate treatment. Congenital or acquired narrowing of the subglottis is the leading ENT cause for recurrent croup (RC) in children. Laryngeal cleft-type 1 is commonly seen in children with recurrent aspiration and CC. Children are usually referred to pulmonologists for wet cough not responding to treatment. Eosinophilic esophagitis (EoE) and GERD should be considered in the differential diagnosis of CC in children with both respiratory symptoms and failure to thrive.Level of Evidence: 2a.

Evaluation of Vancomycin Dosing in Pediatric Cystic Fibrosis Patients.

OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15-20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 ± 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses.

Characterization of a recurrent 3.8kb deletion involving exons 17a and 17b within the CFTR gene.

BACKGROUND: Large deletions within CFTR have been estimated to constitute 1-2% pathogenic alleles, but the occurrence could be much higher in classical cystic fibrosis (CF) patients with one mutation detectable by the routine screening/sequencing work-up. Currently, evaluation of major CFTR rearrangements is not included in the mutation analysis for the reproductive partner of a CF patient/carrier. METHODS: Exon sequencing and Multiplex Ligation-dependent Amplification (MLPA) analyses were used to make a molecular diagnosis of two unrelated CF patients. Long PCR, restriction mapping, cloning, and hot start sequencing were employed to accurately annotate the rearrangement junctions. RESULTS: Both patients had a heterozygous single amino acid deletion mutation identified by sequencing, and a heterozygous deletion of CFTR exons 17a and 17b detected by MLPA. Molecular characterization of the rearrangement breakpoints indicated that the two patients had an identical complex c.2988+1616_c.3367+356del3796ins62 change, flanked by a pair of perfectly inverted repeats of 32 nucleotides. CONCLUSIONS: The c.2988+1616_c.3367+356del3796ins62 complex rearrangement is a recurrent mutation from patients of different ethnic backgrounds. This mutation can be detected through a simple PCR based analysis.

Lung transplantation for childhood diffuse lung disease.

BACKGROUND: Pediatric diffuse lung diseases comprise a heterogeneous group of rare lung disorders which may lead to end stage lung disease and referral for lung transplantation. Previous studies are limited by small numbers of patients with specific forms of diffuse lung disease. Children with all forms of diffuse lung disease who underwent lung transplantation at two pediatric centers were evaluated in terms of several pre- and post-transplant factors and compared to children with other end stage lung disorders. METHODS: A retrospective chart review was performed on all patients transplanted between October 1, 2002 and June 15, 2007 at Texas Children's Hospital and St. Louis Children's Hospital. Multiple pre-transplant characteristics and post-transplant morbidities and mortality were compared between diffuse lung disease, cystic fibrosis, and pulmonary vascular disease groups. RESULTS: There were 31 diffuse lung disease (DLD), 57 cystic fibrosis (CF), and 16 pulmonary vascular disease (PVD) patients included in our analysis. Patients with DLD had significantly higher pre-transplant morbidity including lower percent predicted of forced expiratory volume in first second (P = 0.013) and more patients with pulmonary hypertension (P = 0.001) and hypercapnia (P = 0.031). Compared to CF patients, more DLD and PVD patients required invasive ventilation (P = 0.001) and care in the pediatric intensive care unit (P = 0.001). After transplant, there was a difference among the three groups with regards to number of acute allograft rejections but statistical limitations preclude knowing between which group the difference lies. A difference in time to bronchiolitis obliterans was found between the PVD and CF groups but not when compared to the DLD patients. The three groups had similar time to post-transplant lymphoproliferative disease, rate of infections, and survival. CONCLUSION: Lung transplantation is as successful for patients with end stage diffuse lung disease as compared to other lung transplant candidates.

Bronchiolitis obliterans in children.

PURPOSE OF REVIEW: In this review, we discuss recent advances in our understanding of the etiology, pathology and pathogenesis, clinical presentation, diagnosis, treatment, and outcome of bronchiolitis obliterans in the nontransplant, pediatric population. RECENT FINDINGS: The diagnosis of bronchiolitis obliterans in children can be made with confidence based on clinical presentation, particularly with a history of adenovirus bronchiolitis or pneumonia, fixed obstructive lung disease on pulmonary function testing, and characteristic changes of mosaic perfusion, vascular attenuation, and central bronchiectasis on chest high-resolution computed tomography, thus avoiding the need for lung biopsy in most patients. Patients with postinfectious bronchiolitis obliterans generally have chronic, nonprogressive disease; in contrast, patients with bronchiolitis obliterans from Stevens-Johnson syndrome often have progressive disease that may require lung transplantation. SUMMARY: Bronchiolitis obliterans is a rare form of chronic obstructive lung disease that follows a severe insult to the lower respiratory tract, resulting in fibrosis of the small airways. In the nontransplant pediatric population, adenovirus infection is the most common cause. Treatment is largely supportive and prognosis is mainly related to the underlying cause and to the severity of the initial insult.