Amy G. Filbrun

Longitudinal measures of lung function in infants with bronchopulmonary dysplasia

We previously demonstrated that infants with a history of bronchopulmonary dysplasia (BPD) exhibit airflow obstruction and air trapping. The purpose of this study was to assess longitudinal changes in pulmonary function in infants with a history of BPD over the first 3 years of life, and the relationship to somatic growth. Spirometry was measured using the raised volume rapid thoracoabdominal compression technique, and lung volumes measured by plethysmography. Eighteen infants (mean gestational age ± SD 27.3 ± 2.2 weeks, birthweight 971 ± 259 g) underwent two lung function studies. Average age at first test was 58.8 weeks. Spirometry demonstrated significant reductions in forced expiratory volume in 0.5 sec (FEV0.5, 76.0 ± 15.9% predicted, Z‐score −2.13 ± 1.69), forced expiratory flow at 75% of expired forced vital capacity (FEF75, 54.8 ± 31.1%, −3.58 ± 2.73), and FEF25–75 (67.8 ± 33.3%, −1.79 ± 1.76). Group mean total lung capacity (TLC) was in the low normal range (82.9 ± 13.5% predicted) and residual volume (RV)/TLC was mildly elevated (122.4 ± 38.2% predicted). Repeat testing was performed an average of 32.7 weeks after initial testing. At re‐evaluation, group mean lung volumes and flows tracked at or near their previous values; thus, in general, there was a lack of catch‐up growth. However, compared to infants with below average or average somatic growth (as represented by g/day), infants with above average growth showed significantly greater improvements in percent predicted FVC, FEV0.5, TLC, and RV/TLC (all P < 0.05, ANOVA). We conclude that longitudinal measures of pulmonary function in infants and young children with BPD demonstrate significant airflow obstruction and modest restriction, which tends to persist with time. On the other hand, infants with above average somatic growth showed greater lung growth than their peers. Additional studies examining the effects of various nutritional regimens on lung function are warranted. Pediatr Pulmonol. 2011; 46:369–375.

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

There are limited data assessing bronchodilator responsiveness (BDR) in infants and toddlers with recurrent wheezing, and factors associated with a positive response.

Predictors of early lung function in patients with congenital diaphragmatic hernia

PURPOSE Long-term pulmonary outcomes of congenital diaphragmatic hernia (CDH) have demonstrated airflow obstruction in later childhood. We examined pulmonary function data to assess what factors predict lung function in the first three years of life in children with CDH. METHODS This was a retrospective study of patients treated for CDH who underwent infant pulmonary function testing (IPFT) between 2006 and 2012. IPFT was performed using the raised volume rapid thoracoabdominal compression technique and plethysmography. RESULTS Twenty-nine neonates with CDH had IPFTs in the first 3years of life. Their mean predicted survival using the CDH Study Group equation was 63%±4%. Fourteen infants (48%) required extracorporeal membrane oxygenation (ECMO). The mean age at IPFT was 85.1±5weeks. Airflow obstruction was the most common abnormality, seen in 14 subjects. 12 subjects had air trapping, and 9 demonstrated restrictive disease. ECMO (p=0.002), days on the ventilator (p=0.028), and days on oxygen (p=0.023) were associated with restrictive lung disease. CONCLUSION Despite following a group of patients with severe CDH, lung function revealed mild deficits in the first three years of life. Clinical markers of increased severity (ECMO, ventilator days, and prolonged oxygen use) are correlated with reduced lung function.

Improving nutritional status in a pediatric cystic fibrosis center

The nutritional status of patients with cystic fibrosis (CF) is strongly associated with pulmonary function, respiratory status and survival. Malnutrition could result from a discrepancy between energy needs and food intake while malabsorption results from pancreatic insufficiency which occurs in 85% of people with CF.

Hypervitaminosis A Causing Hypercalcemia in Cystic Fibrosis. Case Report and Focused Review

Hypercalcemia is a rare complication of hypervitaminosis A. We report a pediatric patient with cystic fibrosis (CF) and pancreatic insufficiency who was found to have hypervitaminosis A causing hypercalcemia, complicated by nephrocalcinosis and renal impairment. The patient is a 4-year-old girl with pancreatic-insufficient CF, gastroesophageal reflux, oral aversion, and failure to thrive requiring gastrostomy tube placement. She was prescribed Source CF vitamins, but rarely received the full dose, due to emesis and intolerance. She had routine annual labs that revealed hypercalcemia with elevated blood urea nitrogen and creatinine, which were not present in her previous annual labs. Upon further questioning, her mother reported that she seemed more fatigued for a few weeks, had abdominal pain, and was urinating more frequently. Upon admission to the hospital, laboratory results revealed elevated HCO3, while serum levels of potassium, phosphorus, and albumin were within normal limits. Vitamin D (25-hydroxy) level was low, and vitamin A level was elevated. Extensive metabolic and hormonal workup for the etiology of the hypercalcemia revealed evidence of chronic renal insufficiency and elevated vitamin A levels. She had a renal ultrasound that revealed bilateral nephrocalciosis. Diagnosis of chronic hypervitaminosis A complicated by hypercalcemia was made and was managed by holding vitamin A supplements, aggressive diuresis, and prednisolone. This case emphasizes the importance of regular vitamin A monitoring in patients with CF. There is a wide variability for the lowest intake required to cause toxicity, and the lower limit to cause toxicity has not been determined.

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

BACKGROUND The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials.

Emergency airway and ventilator procedures for community based home care staff validation of an educational program

Children discharged home with tracheostomy and chronic mechanical ventilator support are at high risk for complications and adverse events. Private duty nursing and home respiratory care services are a critical support necessary for successful discharge. The literature suggests that there are opportunities for home care staff (HCS) to improve upon the skills necessary to assess and intervene in an emergency thereby increasing the likelihood of improving long‐term outcomes.

Treatment of Cystic Fibrosis

The treatment of cystic fibrosis (CF) requires a multi-pronged approach to target dysfunction in a number of organ systems. Although the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies heralds a new era in CF care, their full impact on CF remains to be determined, and older patients with CF are likely to still have complications of CF that need to be addressed.

Monitoring and Evaluation of Patients with Cystic Fibrosis

The monitoring of individuals with cystic fibrosis (CF) has become increasingly complex, as the benefits of screening for complications and proactive early intervention have been realized. The era of newborn screening (NBS) has provided a wealth of information that has demonstrated the importance of optimal nutrition early in life. The prognosis of an individual patient is closely tied to his or her nutritional status and, therefore necessitates close attention to growth parameters. Lung disease is an overwhelming cause of morbidity and mortality, and monitoring of lung disease is an essential component of CF care.

Pathophysiology of Cystic Fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane protein that belongs to the family of adenosine triphosphate (ATP) binding cassette proteins. It is expressed in multiple tissues throughout the body, where it plays a key role in the regulation of ion transport across cell membranes in mucosal surfaces [1]. CFTR conducts chloride (Cl) and bicarbonate (HCO3-), and it also appears to reduce sodium (Na) transport through inhibition of the epithelial sodium channel (ENaC). In the absence of CFTR function the loss of ion transport has different effects on different tissues. In the sweat duct, CFTR serves to resorb NaCl from sweat, and in its absence there is excessive salt loss through sweat. In organs such as the pancreas and the liver, loss of ion transport results in viscous mucus secretions and ductal obstruction.