Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Rationale:The clinical pathology describing infants with chronic lung disease of infancy (CLDI) has been limited and obtained primarily from infants with severe lung disease, who either died or required lung biopsy. As lung tissue from clinically stable outpatients is not available, physiological measurements offer the potential to increase our understanding of the pulmonary pathophysiology of this disease. Objectives: We hypothesized that if premature birth and the development of CLDI result in disruption of alveolar development, then infants and toddlers with CLDI would have a lower pulmonary diffusing capacity relative to their alveolar volume compared with full-term control subjects. Methods: We measured pulmonary diffusing capacity and alveolar volume, using a single breath-hold maneuver at elevated lung volume. Subjects with chronic lung disease of infancy (23-29 wk of gestation; n 5 39) were compared with full-term control subjects (n 5 61) at corrected ages of 11.6 (4.8-17.0) and 13.6 (3.2-33) months, respectively. Measurements and Main Results: Alveolar volume and pulmonary diffusing capacity increased with increasing body length for both groups. After adjusting for body length, subjects with CLDI had significantly lower pulmonary diffusing capacity (2.88 vs. 3.23 ml/ min/mm Hg; P 5 0.0004), but no difference in volume (545 vs. 555 ml; P 5 0.58). Conclusions: Infants and toddlers with CLDI have decreased pulmonary diffusing capacity, but normal alveolar volume. These physiological findings are consistent with the morphometric data obtained from subjects with severe lung disease, which suggests an impairment of alveolar development after very premature birth.

Forced expiratory maneuvers generated by rapid thoracic compression have been used to assess airway function in infants. It remains unclear whether flow limitation can be achieved in healthy infants because low pressure transmission across the chest wall and inspiratory effort may limit the maximum transpulmonary pressure developed during the maneuver. We have found that several rapid inflations to a lung volume set at an airway pressure of 30 cmH2O (V80) briefly inhibit respiratory effort and allow forced expiration to proceed from V80 to residual volume. We used a water-filled esophageal catheter to measure isovolume pressure-flow curves in seven healthy infants (3-88 mo). Forced vital capacity (FVC) was defined as the volume between V80 and residual volume. Pressure transmission between the compression jacket and the esophagus decreased with decreasing lung volume and averaged 60 and 37% at 50 and 75% of expired FVC, respectively. Subjects demonstrated plateaus in their isovolume pressure-flow curves at 50% of expired FVC and lower lung volumes. We conclude that this new methodology enables forced expiratory maneuvers to achieve flow limitation in healthy infants over at least the lower portion of their lung volume.

Background Family histories of atopy, as well as histories of atopic dermatitis and food allergy, are important risk factors for an infant to have asthma. Although atopic sensitization appears to contribute to the development of asthma, it is unclear when the airways become involved with the atopic process and whether airway function relates to the atopic characteristics of the infant. Objective We sought to evaluate whether atopic infants without prior episodes of wheezing have increased expired nitric oxide (eNO) levels and heightened airway reactivity. Methods Infants with eczema were recruited, and atopic status was defined by specific IgE levels to foods or aeroallergens and total IgE levels. eNO, forced expiratory flow at 75% exhaled volume (FEF75), and airway reactivity to inhaled methacholine were measured in sedated infants. Airway reactivity was quantified by using the provocative concentration to decrease FEF75 by 30%. Results Median age for the 114 infants evaluated was 10.7 months (range, 2.6–19.1 months). Infants sensitized to egg or milk compared with infants sensitized to neither egg nor milk had lower flows (FEF75: 336 vs 285 mL/s, P < .003) and lower lnPC30 (mg/mL) provocative concentrations to decrease FEF75 by 30% (−0.6 vs −1.2, P < .02) but no difference in eNO levels. Infants with total serum IgE levels of greater than 20 IU/mL had higher eNO levels compared with infants with IgE levels of 20 IU/mL or less (14.6 vs 11.2 ppb, P < .023) but no difference in forced flows or airway reactivity. Conclusions Our findings suggest that atopic characteristics of the infant might be important determinants of the airway physiology of forced expiratory flows, airway reactivity, and eNO.

Background-Childhood asthma is most often characterized by recurrent wheezing, airway hyperreactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory illnesses and atopic sensitization early in life may produce an interaction between innate and acquired immune responses leading to airway inflammation and heightened airway reactivity.

Forced expiratory flows at functional residual capacity (VmaxFRC) by the rapid compression technique and functional residual capacity (FRC) by the helium dilution technique were assessed in 112 normal infants with a mean age of 10.7 months (range, 1.0-31.0). In predicting FRC, log transformation was appropriate and body length was the best predicator. For VmaxFRC, age was a better predictor than length, and logarithmic transformation was not required. In(FRC) = -5.465 + 2.49 x In(length) SD = 0.178; r2 = 0.83 VmaxFRC = -397 + 9.36 x (age) SD = 88; r2 = 0.52 There were no gender differences for FRC or VmaxFRC; however, male infants exposed to passive cigarette smoke tended to have lower flows than male infants not exposed (P < 0.07). This study establishes normative values for VmaxFRC and FRC in infants between 1 and 31 months of age, and suggests that passive cigarette smoke exposure has an adverse effect upon forced expiratory flows in male infants.

Summary Background Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age. Methods Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age. Results We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age. Conclusions While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness.

Parental tobacco smoking is associated with lower airway function and an increased incidence of wheezy respiratory illnesses in infants. We evaluated in 76 healthy infants whether exposure to parental tobacco smoking was associated with airway hyperreactivity, which could contribute to lower airway function and the increased wheezy illnesses. Airway function was measured using the raised-volume rapid thoracic compression technique, and airway reactivity was assessed by methacholine challenge (0.015-10 mg/ml), which was stopped for a more than 30% decrease in forced expiratory flow (FEF)(75) or the final dose with a less than 30% decrease. Parental tobacco smoking was associated with lower baseline airway function (FEF(50), 600 vs. 676 ml/second, p < 0.04; FEF(25-75), 531 vs. 597 ml/second, p < 0.05). Infants exposed to tobacco smoking were approximately half as likely to develop a more than 30% decline in FEF(75) at any given methacholine dose (hazard ratio = 0.4, p = 0.001). In addition, a history of asthma in an extended family member increased the likelihood that an infant would develop a more than 30% decline in FEF(75) (hazard ratio = 1.7, p = 0.04). We conclude that exposure to parental smoking is associated with lower airway function but not increased airway reactivity; however, family history of asthma is associated with heightened airway reactivity.