Agreement between spirometry and impulse oscillometry for lung function assessment in 6-year-old children born extremely preterm and at term.

BACKGROUND: Extremely preterm birth is a risk factor for reduced lung function later in life, and clinical follow-up from early childhood is recommended. Dynamic spirometry is the most widely used method to assess airway obstruction, but impulse oscillometry (IOS) may be an alternative method that is easier to perform in young children. The feasibility and agreement between spirometry and IOS outcome variables has not been investigated in children born extremely preterm. AIM: To determine the feasibility of and correlation between spirometry and IOS in pre-school children born extremely preterm. METHODS: Spirometry and IOS were performed in 6-year-old children born extremely preterm (n = 88) and age-matched term controls (n = 84) in Stockholm, Sweden. Correlations between spirometry and IOS outcome variables were analyzed using Pearson's partial correlation, adjusting for height. RESULTS: Success rate for spirometry (60%) was lower than for IOS (93%) but did not differ significantly between the preterm and term groups (56% and 64% for spirometry, P = .25; and 92% and 94% for IOS, P = .61). Correlations between spirometry and IOS outcomes were at best moderate (Spearman's r = -0.31 to -0.56). Normal IOS identified 69% to 90% of those with normal spirometry. A negative predictive value of 90% was found for R5-R20 versus FEV0.75 /FVC, suggesting that IOS may be used to exclude obstructive airway disease as measured by spirometry. CONCLUSION: IOS is a more feasible method than spirometry to assess lung function in young children irrespective of gestational age at birth and could be considered an alternative in children who cannot perform spirometry.

Early life determinants of lung function change from childhood to adolescence.

RATIONALE: Little is known about how perinatal and childhood factors influence lung function change between childhood and adolescence. OBJECTIVES: To investigate possible early life predictors of change in FEV1 between age 8 and 16 years. In addition, to investigate possible predictors of having persistently low lung function (FEV1 <25th percentiles both at age 8 and 16) up to adolescence. METHODS: The BAMSE birth cohort study collected data throughout childhood on environmental factors, individual characteristics, and spirometric measures at 8 and 16 years (n = 1425). Associations between early life predictors (n = 31) and FEV1 increase between 8 and 16 years were assessed with linear regression. Predictors of having persistently low lung function were examined. RESULTS: Few factors were consistently associated with altered lung function growth, although low birth weight, asthma heredity (paternal), secondhand smoke in infancy, and season of birth had a significant impact (p-value ≤0.01). The majority of subjects stayed however within the same category of lung function between ages 8 and 16 years (in total 821/1425 = 58%). Predictors associated with having persistently low lung function were gestational age, secondhand smoke (at 2 and 8 years of age), and factors related to lower respiratory tract infections in infancy. CONCLUSIONS: In summary, rather few exposures in childhood were identified to have a significant impact on lung function growth between childhood and adolescence. Our data support previous study findings indicating that lung function development is influenced by factors before birth and in infancy, including second hand tobacco smoke.

Tobacco smoke exposure in early life and adolescence in relation to lung function.

Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years.The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295).Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of -1.1% (95% CI -2.0 to -0.2%). IOS demonstrated greater resistance at 5-20 Hz (R5-20) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV1/FVC ratios of -0.9% (95% CI -1.8 to -0.1%) and increased resistance of 6.5 Pa·L-1·s (95% CI 0.7 to 12.2 Pa·L-1·s) in R5-20 Comparable associations for FEV1/FVC ratio were observed for cotinine concentrations, using ≥12 ng·mL-1 as a cut-off for adolescent smoking.Maternal smoking during pregnancy was associated with lower FEV1/FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV1/FVC ratios and increased peripheral airway resistance.

Body mass index status and peripheral airway obstruction in school-age children: a population-based cohort study.

BACKGROUND: Few large prospective studies have investigated the impact of body mass index (BMI) on lung function during childhood. METHODS: Using data collected between 2002 and 2013, we analysed associations between BMI status and lung function (assessed by spirometry) from 8 to 16 years, as well as cross-sectional associations with small airway function (impulse oscillometry) at 16 years in the BAMSE cohort (n=2889). At 16 years, cross-sectional associations with local and systemic inflammation were investigated by analysing FENO, blood eosinophils and neutrophils. RESULTS: Overweight and obesity at 8 years were associated with higher FVC, but lower FEV1/FVC ratio at 8 and 16 years. In boys, but not girls, obesity at 8 years was associated with a further reduction in FEV1/FVC between 8 and 16 years. In cross-sectional analyses, overweight and obesity were associated with higher frequency dependence of resistance (R5-20) and larger area under the reactance curve (AX0.5) at 16 years. Increased blood neutrophil counts were seen in overweight and obese girls, but not in boys. No association was found between BMI status and FENO. Persistent, but not transient, overweight/obesity between 8 and 16 years was associated with higher R5-20 and AX0.5 and lower FEV1/FVC (-2.8% (95% CI -4.1 to -1.2) in girls and -2.7% (95% CI -4.4 to -1.1) in boys) at 16 years, compared with persistent normal weight. CONCLUSION: In childhood and adolescence, overweight and obesity, particularly persistent overweight, were associated with evidence of airway obstruction, including the small airways.

Lung function after extremely preterm birth-A population-based cohort study (EXPRESS).

BACKGROUND AND OBJECTIVES: Follow-up studies of children and young adults born very-to-moderately preterm show persistent and significant lung function deficits. The aim of the study was to determine lung function and airway mechanics in school-aged children born in 2004 to 2007 and extremely preterm (after 22-26 weeks of gestation). METHODS: In a population-based cohort of children born extremely preterm and controls born at term (n = 350), follow-up at 6½-years-of-age was performed using spirometry and impulse oscillometry. Associations to gestational age, smallness for gestational age (SGA), and bronchopulmonary dysplasia (BPD) were assessed. RESULTS: Children born extremely preterm had lower forced vital capacity (FVC, z-score: -0.7, 95%CI: -1.0;-0.4), forced expiratory volume (FEV1 , z-score: -1.1, 95%CI: -1.4; -0.8), higher frequency-dependence of resistance (R5-20 , 0.09, 95%CI: 0.05; 0.12 kPa · L-1 · s-1 ) and larger area under the reactance curve (AX, 0.78, 95%CI: 0.49; 1.07 kPa · L-1 ) than controls. In children born at 22-24 weeks of gestation, 24% had FVC and 44% had FEV1 below the lower limit of normal. SGA and severe BPD only marginally contributed to pulmonary outcomes. Asthma-like disease was reported in 40% of extremely preterm children and 15% of controls. CONCLUSION: Many children born extremely preterm have altered airway mechanics and significant obstructive reduction in lung function. This warrants consideration for treatment and continued follow-up.

Lung function development after preterm birth in relation to severity of Bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a strong risk factor for respiratory morbidity in children born preterm. Our aims were to evaluate lung function in adolescents born preterm with and without a history of BPD, and to assess lung function change over time from school age. METHODS: Fifty-one individuals born in Stockholm, Sweden between gestational ages 24 to 31 weeks (23 neonatally diagnosed with respiratory distress syndrome (RDS) but not BPD, and 28 graded as mild (n = 17), moderate (n = 7) or severe (n = 4) BPD) were examined in adolescence (13-17 years of age) using spirometry, impulse oscillometry (IOS), plethysmography, and ergospirometry. Comparison with lung function data from school age (6-8 years of age) was also performed. RESULTS: Adolescents with a history of BPD had lower forced expiratory volume in 1 s (FEV1) compared to those without BPD (-0.61 vs.-0.02 z-scores, P < 0.05), with lower FEV1 values significantly associated with BPD severity (P for trend 0.002). Subjects with severe BPD had higher frequency dependence of resistance, R5-20, (P < 0.001 vs. non-BPD subjects) which is an IOS indicator of peripheral airway involvement. Between school age and adolescence, FEV1/FVC z-scores decreased in all groups and particularly in the severe BPD group (from -1.68 z-scores at 6-8 years to -2.74 z-scores at 13-17 years, p < 0.05 compared to the non-BPD group). CONCLUSIONS: Our results of spirometry and IOS measures in the BPD groups compared to the non-BPD group suggest airway obstruction including involvement of peripheral airways. The longitudinal result of a decrease in FEV1/FVC in the group with severe BPD might implicate a route towards chronic airway obstruction in adulthood.

Lung Function at 8 and 16 Years After Moderate-to-Late Preterm Birth: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: Knowledge regarding lung function after moderately preterm birth is limited. We therefore investigated lung function at early school age and adolescence among children born moderately preterm. METHODS: Data were used from the Swedish prospective birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology study; N = 4089), with a 4.8% prevalence of moderate to late preterm birth defined as a gestational age of 32 to 36 weeks. Participants underwent spirometry at ages 8 and 16 years, and impulse oscillometry additionally at age 16 years. In total, 2621 children (149 preterm and 2472 term) provided lung function data. RESULTS: At age 8 years, adjusted forced expiratory volume in 1 second was lower in preterm female subjects (-64 mL [95% confidence interval (CI): -118 to -10]) compared with term female subjects but not in preterm male subjects. At age 16 years, both genders in the preterm group demonstrated lower forced expiratory volume in 1 second (female subjects: -116 mL [95% CI: -212 to -20]; male subjects: -177 mL [95% CI: -329 to -25]) compared with the term group. For the preterm group, impulse oscillometry demonstrated higher adjusted resistance at 5 Hz (female subjects: 31.3 Pa·L(-1)·s(-1) [95% CI: 6.3 to 56.3]; male subjects: 34.9 Pa·L(-1)·s(-1) [95% CI: 12.0 to 57.7]) and frequency dependence of resistance (resistance at 5 and 20 Hz) for male subjects (20.9 Pa·L(-1)·s(-1) [95% CI: 9.8 to 31.9]) compared with the term group. CONCLUSIONS: Measures of airway function assessed in adolescence were reduced in children born moderate to late preterm, and no catch-up in lung function between ages 8 and 16 years was observed.

Early-Life Exposure to Traffic-related Air Pollution and Lung Function in Adolescence.

RATIONALE: Exposure to air pollution during infancy has been related to lung function decrements in 8-year-old children, but whether the negative effects remain into adolescence is unknown. OBJECTIVES: To investigate the relationship between long-term air pollution exposure and lung function up to age 16 years. METHODS: A total of 2,278 children from the Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) performed spirometry at age 16 years. Levels of outdoor air pollution from local road traffic were estimated (nitrogen oxides [NOx] and particulate matter with an aerodynamic diameter of <10 µm [PM10]) for residential, daycare, and school addresses during the lifetime using dispersion modeling. Associations between exposure in different time windows and spirometry indexes were analyzed by linear regression and mixed effect models. MEASUREMENTS AND MAIN RESULTS: Exposure to traffic-related air pollution during the first year of life was associated with FEV1 at age 16 years of -15.8 ml (95% confidence interval [CI], -33.6 to 2.0 for a 10 µg/m(3) difference in NOx), predominately in males (-30.4 ml; 95% CI, -59.1 to -1.7), and in subjects not exposed to maternal smoking during pregnancy or infancy. Later exposures appeared to have had an additional negative effect. High exposure during the first year of life was also associated with odds ratios for FEV1 and FVC less than the lower limit of normal (LLN) (defined as a z-score < -1.64 SD) of 3.8 (95% CI, 1.3-10.9) and of 4.3 (95% CI, 1.2-15.0), respectively. The results for PM10 were similar to those for NOx. CONCLUSIONS: Exposure to traffic-related air pollution in infancy is negatively associated with FEV1 at age 16 years, leading to increased risk of clinically important deficits.

Lung function at 6 and 18 months after preterm birth in relation to severity of bronchopulmonary dysplasia.

UNLABELLED: Many preterm infants with bronchopulmonary dysplasia (BPD) demonstrate impaired lung function and respiratory symptoms during infancy. The relationships between initial BPD severity, lung function and respiratory morbidity are not fully understood. We aimed to investigate the association between BPD severity and subsequent lung function and whether lung function impairment is related to respiratory morbidity. STUDY DESIGN AND METHODS: In this longitudinal cohort study, 55 infants born preterm (23-30 weeks of gestation) with mild or moderate/severe BPD, based on oxygen requirement at 36 gestational weeks, were followed up at 6 and 18 months postnatal age. Respiratory symptoms, such as recurrent or chronic chough and wheeze, were noted and patient records were scrutinized. Lung function was assessed by passive lung mechanics, whole body plethysmography, and tidal and raised volume rapid thoraco-abdominal compression techniques. Results were related to published normative values. RESULTS: Besides residual functional capacity (FRC) and respiratory system compliance (Cso ) assessed at 18 months, all measures of lung function were significantly below normative values. Moderate/severe BPD differed significantly from mild BPD only with respect to reduced Cso . At follow-up at 6 and 18 months, participants with respiratory symptoms showed lower; maximal forced expiratory flow at FRC (V'maxFRC) (P = 0.006, P = 0.001), forced mid-expiratory flows (MEF50 ) (P = 0.006, P = 0.048), and Cso (P = 0.004, P = 0.015) as compared to participants without symptoms. CONCLUSIONS: In the present study BPD severity did not predict lung function, but may be associated with impaired alveolarization, indicated by reduced Cso . Respiratory morbidity was associated with reduced airway function and respiratory compliance in infancy after preterm birth.

Infant wheeze, comorbidities and school age asthma.

BACKGROUND: Factors associated with early onset of wheeze have been described, but there is limited knowledge on which of these infant wheezers who will have developed asthma in school age. The aim was to identify clinical risk factors for asthma in the 8-yr-old children that wheezed during infancy in a population-based setting. METHODS: Three thousand two hundred and fifty-one children from a population-based birth cohort followed prospectively from infancy until age 8 yr were included in the study. Data were analyzed using multivariate logistic regression analysis. RESULTS: Parents reported any wheeze episode before age 2 yr in 823 subjects (25%). Infant wheezers had an almost fourfold risk of asthma at age 8 [adjusted odds ratio (aOR) 3.68, 95% CI 2.74-4.96], equivalent to an asthma prevalence of 14% compared with 4% among non-wheezers (p < 0.001). After adjustments for sex, exposure to tobacco smoke and indoor dampness/mould, allergic heredity (aOR 1.53, 95% CI 1.02-2.30), increased frequency of wheeze (aOR 3.41, 95% CI 2.09-5.56 for children with ≥3 episodes compared with ≤2 episodes during the first 2 yr of life), infant eczema (aOR 2.31, 95% CI 1.52-3.49), and recurrent abdominal pain (aOR 2.33, 95% CI 1.30-4.16) remained risk factors for school age asthma in the infant wheezing group. CONCLUSIONS: Among infant wheezers, allergic heredity, increased severity of wheeze, infant eczema, and recurrent abdominal pain were independent risk factors for asthma at age 8 yr. Among children with three or four of these risk factors, 38% had asthma at school age.

Obstructive lung disease in children with mild to severe BPD.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common cause of respiratory insufficiency in children born very premature. OBJECTIVES: The purpose of this study was to examine the impact of the severity of BPD on pulmonary morbidity at school age, as measured by conventional spirometry and impulse oscillometry. We also studied the association between changes in lung function and structural changes in the lungs of children with BPD via High-Resolution Computed Tomography (HRCT). Finally we studied the prevalence of atopy associated with BPD. METHODS: We studied 60 very low birth weight (VLBW) children, 28 with respiratory distress syndrome (RDS) who did not develop BPD ("preterm non-BPD") and 32 with RDS who developed BPD. The severity of BPD was graded as mild, moderate or severe. Follow-up at age 6-8 years consisted of spirometry, oscillometry, thoracic HRCT, allergy skin-prick test, blood samples and a questionnaire. RESULTS: All children with BPD showed some evidence of impaired lung function (more negative reactance, FEV1<80% predicted, greater reversibility), although less than half of these children were symptomatic. The majority of children with BPD (19/26) showed abnormalities on HRCT. There was no evidence that atopy was associated with BPD. CONCLUSIONS: Children with mild BPD exhibited similar impairments in respiratory mechanics and lung structure to those diagnosed with moderate BPD. The widespread involvement of the peripheral airways suggests that all children diagnosed with BPD are potentially at risk of developing chronic obstructive pulmonary disease later in life.