Rationale: Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. Objectives: To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. Methods: Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV_0.5, and forced expiratory flows at 75% of exhaled vital capacity (FEF₇₅) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. Measurements and Main Results: In the CF group, the deficit in FEV_0.5 z score increased by −0.77 (95% confidence interval, −1.14 to −0.41; P < 0.001) with each year of age. The mean FEV_0.5 z score did not differ between infants with CF and healthy control subjects less than 6 months of age (−0.06 and 0.02, respectively; P = 0.87). However, the mean FEV_0.5 z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF₇₅ followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. Conclusions: Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

Rationale: Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. Objectives: We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Methods: Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0–2 yr) and again at early school age (4–8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Measurements and Main Results: Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], –15.9 to –6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). Conclusions: The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

Electronic cigarette usage is increasing worldwide, yet there is a paucity of information on the respiratory health effects of electronic cigarette aerosol exposure. This study aimed to assess whether exposure to electronic cigarette (e-cigarette) aerosol would alter lung function and pulmonary inflammation in mice and to compare the severity of any alterations with mice exposed to mainstream tobacco smoke. Female BALB/c mice were exposed for 8 wk to tobacco smoke, medical air (control), or one of four different types of e-cigarette aerosol. E-cigarette aerosols varied depending on nicotine content (0 or 12 mg/ml) and the main excipient (propylene glycol or glycerin). Twenty-four hours after the final exposure, we measured pulmonary inflammation, lung volume, lung mechanics, and responsiveness to methacholine. Mice exposed to tobacco cigarette smoke had increased pulmonary inflammation and responsiveness to methacholine compared with air controls. Mice exposed to e-cigarette aerosol did not have increased inflammation but did display decrements in parenchymal lung function at both functional residual capacity and high transrespiratory pressures. Mice exposed to glycerin-based e-cigarette aerosols were also hyperresponsive to methacholine regardless of the presence or absence of nicotine. This study shows, for the first time, that exposure to e-cigarette aerosol during adolescence and early adulthood is not harmless to the lungs and can result in significant impairments in lung function.

Background: Exhaled nitric oxide (FE_NO) is raised in asthmatic children, but there are inconsistencies in the relationship between FE_NO and characteristics of asthma, including atopy, increased airway responsiveness (AR), and airway inflammation. The aim of this study was to investigate the relationship between FE_NO and asthma, atopy, and increased AR in children. Methods: One hundred and fifty five children (79 boys) of mean age 11.5 years underwent an assessment that included FE_NO measurements, spirometric tests, inhaled histamine challenge, and a skin prick test. Blood was collected for eosinophil count. Current and past asthma like symptoms were determined by questionnaire. Results: In multiple linear regression analyses FE_NO was associated with atopy (p<0.001), level of AR (p = 0.005), blood eosinophil count (p = 0.007), and height (p = 0.002) but not with physician diagnosed asthma (p = 0.1) or reported wheeze in the last 12 months (p = 0.5). Separate regression models were conducted for atopic and non-atopic children and associations between FE_NO and AR, blood eosinophils and height were only evident in atopic children. Exhaled NO was raised in children with a combination of atopy and increased AR independent of symptoms. Conclusion: Raised FE_NO seems to be associated with an underlying mechanism linking atopy and AR but not necessarily respiratory symptoms.

Objective: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation. Design, setting and participants: Using the Western A...