Gregory J. Redding

Bronchiectasis in Alaska Native children: Causes and clinical courses†

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis.

Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis

Patients with cystic fibrosis (CF) frequently experience pulmonary exacerbations that may lead to a faster subsequent decline in pulmonary function; however, this relationship has not been clearly established. The purpose of this study was to determine the association between the frequency of pulmonary exacerbations and subsequent forced expiratory volume in 1 sec (FEV1) decline in adults and children with CF.

Chronic Wet Cough: Protracted Bronchitis, Chronic Suppurative Lung Disease and Bronchiectasis

The role of persistent and recurrent bacterial infection of the conducting airways (endobronchial infection) in the causation of chronic respiratory symptoms, particularly chronic wet cough, has received very little attention over recent decades other than in the context of cystic fibrosis (CF). This is probably related (at least in part) to the (a) reduction in non‐CF bronchiectasis in affluent countries and, (b) intense focus on asthma. In addition failure to characterize endobronchial infections has led to under‐recognition and lack of research. The following article describes our current perspective of inter‐related endobronchial infections causing chronic wet cough; persistent bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis. In all three conditions, impaired muco‐ciliary clearance seems to be the common risk factor that provides organisms the opportunity to colonize the lower airway. Respiratory infections in early childhood would appear to be the most common initiating event but other conditions (e.g., tracheobronchomalacia, neuromuscular disease) increases the risk of bacterial colonization. Clinically these conditions overlap and the eventual diagnosis is evident only with further investigations and long term follow up. However whether these conditions are different conditions or reflect severity as part of a spectrum is yet to be determined. Also misdiagnosis of asthma is common and the diagnostic process is further complicated by the fact that the co‐existence of asthma is not uncommon. The principles of managing PBB, CSLD and bronchiectasis are the same. Further work is required to improve recognition, diagnosis and management of these causes of chronic wet cough in children. Pediatr Pulmonol. 2008; 43:519–531.

Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis

We sought to define objective indicators of the resolution of Pseudomonas aeruginosa endobronchial infection in patients with cystic fibrosis. We prospectively studied 75 patients admitted for treatment of a pulmonary exacerbation and quantitated sputum bacterial density, DNA content, and the concentration of albumin and total protein in sputum, and compared these values with clinical evaluation. Eleven of the 75 patients had systemic signs, fever, and leukocytosis, which we arbitrarily defined as due to endobronchial infection. At the end of hospitalization, these 11 patients were afebrile, had peripheral leukocyte counts in the normal range, and were judged improved. Sputum P. aeruginosa density, DNA content, and total protein content on admission were similar in the two illness groups. Hospitalization and parenteral antibiotic administration for an average of 14.6 days were associated with improved pulmonary function in all 75 subjects (P values for forced vital capacity, forced expiratory volume at 1 second, and peak expiratory flow rate were all less than 0.001). With improvement, there was a decrease in sputum P. aeruginosa density (mean of both groups decreased from 10(7.80) CFU/g on admission to 10(5.96) CFU/g; P less than 0.001), and a decreased DNA concentration (overall mean 4.73 +/- 4.75 on admission to 2.76 +/- 2.49 mg/g; P less than 0.002). The decrease in sputum total protein concentration for both groups was not significant (overall mean 60.5 +/- 48.4 to 43.9 +/- 38.2 mg/g; P = 0.06). Sputum albumin concentrations did not change in either group. We conclude that in cystic fibrosis subjects with a pulmonary exacerbation, bacterial density, sputum DNA and protein content decrease with hospitalization and parenteral antibiotic therapy. At the end of treatment, these indices of sputum infection and inflammation correlate with improved pulmonary function and clinical improvement. These changes are independent of the presence or absence of fever on admission.

Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis.

Lung function (FEV1) generally improves during treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). However, it is unclear how often return to previous baseline FEV1 is achieved.

Comparison of a β-lactam alone versus β-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis

We determined whether a β-lactam and an aminoglycoside have efficacy greater than a β-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. Study design: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. Results: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P = .034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P < .001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. Conclusion: We conclude that the combination of a β-lactam and an aminoglycoside produces a longer clinical remission than a β-lactam alone and slightly better initial improvement. (J Pediatr 1999;134:413-21)

Safety and tolerability of cold-adapted influenza virus vaccine in children and adolescents with asthma

Background. Influenza infections can cause severe respiratory disease in high risk persons such as those with asthma, but immunization rates for high risk groups remain suboptimal. An investigational influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) administered by intranasal spray was shown previously to be effective in healthy adults and healthy children. Purpose. To assess the safety and tolerability of CAIV-T in subjects 9 years of age and older with moderate to severe asthma. Methods. In this randomized, double blind, placebo-controlled study, spirometry was performed twice before vaccination to establish a baseline forced expiratory volume at 1 s (FEV1) and once 2 to 5 days thereafter. The primary outcome index was the percent change in percent predicted FEV1 before and after vaccination. Peak flows, clinical asthma symptom scores and nighttime awakening scores were measured daily from 7 days pre- to 28 days postvaccination. Results. The primary outcome index (percentage change in percent predicted FEV1) was not different between the two groups (0.2%vs. 0.4% for the treatment and placebo groups, respectively;P = 0.78). Secondary outcomes did not differ between the two groups; these included the number of subjects with a decrease in FEV1 ≥15% from baseline, reductions in peak flows ≥15%, ≥30% or ≥2 sd below baseline, use of beta-adrenergic rescue medications, asthma exacerbations and clinical asthma symptom scores before and after vaccination. The same proportion of subjects in each group experienced postvaccination symptoms within 10 days (92% and 91%, respectively;P = 1.0). No serious adverse event occurred. Conclusion. CAIV-T was generally safe and well-tolerated in children and adolescents with moderate to severe asthma.

Childhood asthma hospitalization risk after cesarean delivery in former term and premature infants

BACKGROUND Cesarean delivery modifies infant gut bacterial flora composition, which may result in hindered tolerance to allergenic substances, thereby increasing the risk of asthma in accordance with the hygiene hypothesis. Results of previous studies regarding an association between birth route and asthma are conflicting, and these studies have not evaluated some potential confounding effects, including prematurity and maternal asthma. OBJECTIVE To determine whether cesarean delivery in full-term and premature infants increases the risk of subsequent childhood asthma hospitalization. METHODS We conducted a case-control study using the Washington State Birth Events Record Database linked to statewide hospitalization data. The study included 2,028 children hospitalized for asthma (cases) and 8,292 age-matched controls. RESULTS Cesarean delivery was modestly associated with an increased risk of asthma hospitalization (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.39). However, when analyzed separately, there was an association between cesarean delivery and asthma hospitalization in premature infants (OR, 1.90; 95% CI, 1.09-3.02) but not in full-term infants (OR, 1.15; 95% CI, 0.97-1.34). CONCLUSIONS Cesarean delivery was associated with subsequent asthma hospitalization only in premature infants. Because mothers with asthma are reported to have increased rates of cesarean delivery and premature delivery, other factors in addition to the hygiene hypothesis, including genetic and in utero influences associated with maternal asthma, may contribute to the increased risk of asthma in premature infants.

Early changes in pulmonary function after vertical expandable prosthetic titanium rib insertion in children with thoracic insufficiency syndrome.

BACKGROUND The vertical expandable prosthetic titanium rib (VEPTR) has been inserted in children with thoracic insufficiency syndrome for the last decade to expand and support the chest and allow for further lung growth. There are minimal published data evaluating the postoperative change in lung function after VEPTR insertion. We hypothesize that there will be a significant increase in lung function after VEPTR insertion, and the earlier the insertion, the greater the improvement. METHODS The Chest Wall Disorders Study Group Database, containing data before and after VEPTR insertion from 7 different centers, was queried for spirometry and lung volume measurements, and the data were analyzed to assess the short-term effect on lung function of VEPTR placement. RESULTS There was a statistically significant decrease in forced vital capacity, forced expiratory volume in 1 second as a percent of predicted, an increase in residual volume (RV) that did not reach statistical significance, and there was no change in total lung capacity at the first postoperative visit (7.7 +/- 4.8 months). There was a significant decrease in Cobb angle. There was no correlation between absolute change in any pulmonary function and Cobb angle age at the time of surgery. CONCLUSIONS Although there is a clinically and radiographically apparent expansion of the thorax after VEPTR insertion, there is no similar improvement in lung volume, and instead there is a decrease in forced vital capacity and increase in residual volume, the explanation for which requires further study. This lack of change in pulmonary function after VEPTR insertion suggests that the benefit of VEPTR insertion may lie more in stabilizing the thorax and improving respiratory mechanics measured in other ways.

The Asthma Outreach Project: A Promising Approach to Comprehensive Asthma Management

We describe a pilot system of coordinated asthma care emphasizing home visits by a community-based lay worker collaborating with a pediatrician, pharmacist, and public health nurse. Study participants included 23 low-income children with moderate to severe asthma and their families at an inner-city pediatric clinic. This system was successfully implemented, and client satisfaction was extremely high. Utilization review showed a reduction in hospitalizations, emergency department visits, and unscheduled clinic visits, and an increase in follow-up clinic visits. This model of care may reduce unscheduled service use and deserves further study as an alternative for asthma management among similar patient populations.