Use of the forced oscillation technique to detect bronchodilation in children: experience from the Schneider Children's Medical Center of Israel.

BACKGROUND: The forced oscillation technique is a noninvasive and effort-independent technique that is well suited for lung function measurement in young children. FOT employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers. OBJECTIVES: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy. METHODS: Forty-six children (median age 4.9 years, range 1.8-18.3) attending the pulmonary clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed. RESULTS: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r2 = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry. CONCLUSIONS: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years old. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

Increasing nontuberculous mycobacteria infection in cystic fibrosis.

BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging infections in the CF population. AIMS: To assess NTM infection prevalence and associated features in our CF clinic population. METHODS: Patient records, 2002-2011, were reviewed for NTM infection. FEV1, pancreatic function, sputum microbiology, and serum cytokines were compared in patients with and without NTM infection. RESULTS: Incidence rate of NTM infection increased from 0 in 2002 to 8.7% in 2011 (p<0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to 14.5% (16/110) in 2011 (p=0.05). Prevalence of chronic NTM lung disease has decreased somewhat since a peak in 2009, with institution of aggressive triple therapy. Of NTM-infected compared to uninfected patients, 88.2% vs. 60.3% had a known 'severe' CFTR genotype (p=0.04), 88.2% vs. 58.9% were pancreatic insufficient (p=0.02); 70.6% vs. 43.8% had chronic Pseudomonas aeruginosa (p=0.06); 75% vs. 32% had Aspergillus infection (p=0.007) and 23.5% vs 2.7% had allergic bronchopulmonary aspergillosis (p=0.01). Patients infected with Mycobacterium abscessus had increased TGF-ß, TNF-α, IL-1ß, IL-2, IL-4 and IL-5 levels (p<0.05). There was no difference in cytokine levels for all NTM infected compared to uninfected patients. M. abscessus comprised 46% of all NTM infections. Comparing M. abscessus versus other NTM, duration was 10.5 (1-118) months versus 1 (1-70) month, median (range) (p=0.004); lung disease occurred in 69% versus 17% (p=0.0004), with sputum conversion in 4/11 versus 5/6, respectively (NS). CONCLUSIONS: NTM incidence and prevalence have increased dramatically in our CF clinic, associated with a severe CF genotype and phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection despite therapy. There has been some decrease in the prevalence of NTM lung disease since 2009.

Effectiveness of long-term routine pulmonary function surveillance following pediatric hematopoietic stem cell transplantation.

INTRODUCTION: Pulmonary complications following hematopoietic stem cell transplantation (HSCT) are common and often subclinical. Thus, periodic pulmonary function testing (PFT) is mandatory. This study sought to evaluate the effectiveness of long-term PFT surveillance for children undergoing HSCT and identify potential risk factors. METHODS: We reviewed long-term PFT for HSCT patients at a tertiary pediatric center. Inclusion criteria were PFT prior to and at least once following HSCT. RESULTS: Fifty-seven patients performed 202 spirometry and 193 plethysmographic maneuvers; 41 were tested during the first year after HSCT, but only 29 were evaluated consistently long term (2-12 years). FVC and FEV(1) decreased gradually suggesting a restrictive ventilatory defect: FVC % predicted [mean ± SD] dropped from 91 ± 14% to 85 ± 17% after 0-24 months and 80 ± 19% beyond 2 years (P = 0.01) whereas FEV(1) dropped from 95 ± 16% to 88 ± 19% and 82 ± 20%, respectively (P = 0.002). A slight reduction in TLC was observed. Those undergoing allogeneic HSCT had a greater decline in FVC (P = 0.025) and FEV(1) (P = 0.025) as did those conditioned with radiation, regarding both FVC (P = 0.003) and FEV(1) (P = 0.002). Decline occurred earlier (≤2 years) after chemotherapy compared with radiation. Seven children had severe irreversible obstruction at >2 years despite therapeutic intervention. CONCLUSIONS: Most survivors of childhood HSCT maintain almost normal pulmonary function although mild restrictive lung disease may develop, particularly following allogeneic HSCT and conditioning with radiation. Severe airways obstruction developed in a small minority. The surveillance protocol for PFT needs to be followed more stringently to enable intervention possibly before early subclinical changes progress and become irreversible.

Encouraging pulmonary outcome for surviving, neurologically intact, extremely premature infants in the postsurfactant era.

OBJECTIVE: The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era. METHODS: We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV1 by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance. RESULTS: Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV1 % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01). CONCLUSIONS: Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.