Cow's milk allergy as a predictor of bronchial hyperresponsiveness and airway inflammation at school age.

BACKGROUND: Cow's milk allergy (CMA) has been found to be associated with an increased incidence of asthma at school age. However, prospective population-based studies of CMA and the development of airway inflammation and bronchial hyperresponsivess (BHR) are lacking. OBJECTIVE: The aims of this study was to evaluate CMA as a risk factor for BHR and airway inflammation presented later in childhood. METHODS: We followed prospectively 118 children with CMA and invited them to a clinical visit at a mean age of 8.6 years including the measurement of exhaled nitric oxide (FE(NO) ) and bronchial challenge with histamine. Ninety-four patients and 80 control subjects from the same cohort participated. RESULTS: At school age, children with a history of CMA had higher FE(NO) levels (P=0.0009) and more pronounced responsiveness to histamine (P=0.027) than their controls. Stratified analysis showed a significant difference only in IgE-positive CMA. Multinomial logistic regression analysis showed that IgE-positive CMA [odds ratio (OR) 3.51; 95% confidence intervals (CI) 1.56-7.90; P=0.002] and a history of wheeze during the first year of life (OR 2.81; 95% CI 1.16-6.84; P=0.023) were independent explanatory factors for increased FE(NO) , and IgE-positive CMA (OR 3.37; 95% CI 1.03-10.97; P=0.044) and parental smoking (OR 3.41; 95% CI 1.14-10.22; P=0.028) for increased BHR, whereas for IgE-negative CMA, no associations with FE(NO) or BHR were found. In the CMA group, those exposed to CM very early at the maternity hospital, had less BHR (P=0.002). CONCLUSIONS: Compared with their controls, children with a history of IgE-positive CMA show signs of airway inflammation, expressed as higher FE(NO) , and more pronounced bronchial responsiveness to histamine at school age. In contrast to IgE-negative CMA, IgE-positive CMA is a significant predictor of increased FE(NO) and BHR at school age. Very early exposure to CM was associated with less BHR.

Clinical findings associated with abnormal lung function in children aged 3-26 months with recurrent respiratory symptoms.

AIM: To evaluate whether there are any associations between parentally reported symptoms, clinical findings and lung function in young children with recurrent lower respiratory tract symptoms. METHODS: In 2000-2003, 148 children, aged 3-26 months, with recurrent lower respiratory tract symptoms underwent physical examination, investigation of a chest radiograph, whole body plethysmography and skin prick testing to common food and inhalant allergens. RESULTS: Lung function was considered abnormal (i.e. functional residual capacity z-score of > or =1.65 and/or specific conductance z-score of < or =-1.65) in 83 (56%) children. Findings of increased work of breathing (p < 0.001) and nonspecific noisy breathing sounds (p < 0.001) in the physical examination, as well as an abnormal chest radiograph (p = 0.028) were independently associated with abnormal lung function, explaining up to 34% of the variation in lung function. In contrast, parentally reported respiratory symptoms, environmental exposures or atopic trait were not associated with lung function abnormalities. CONCLUSION: The results of this study emphasize the importance of the meticulous clinical examination in the evaluation of early childhood respiratory disorders. As physical examination alone cannot predict lung function abnormalities reliably in preschool children with troublesome respiratory symptoms, lung function testing may be considered in such patients to obtain additional objective information.

Budesonide improves decreased airway conductance in infants with respiratory symptoms.

OBJECTIVE: Inhaled corticosteroids (ICS) are commonly used to treat wheezing disorders in children, but few studies have investigated the effect of ICS on lung function in infants. We evaluated the efficacy of inhaled budesonide for decreased specific airway conductance (sGaw) as an indication of bronchial obstruction in very young children with recurrent cough and/or wheeze. PATIENTS, DESIGN AND INTERVENTIONS: Functional residual capacity (FRC) and sGaw of steroid-naive children aged 3-26 months with respiratory symptoms were measured using an infant whole-body plethysmograph. Clinically indicated bronchoscopy was performed in 79% of the patients to exclude anatomical abnormalities before randomisation. Children with abnormal lung function and respiratory symptoms were randomised into two treatment groups, receiving either inhaled budesonide (400 microg/day) or placebo with NebuChamber for 6 weeks. Inhaled terbutaline 0.25 mg/dose was used as a rescue medication. Lung function measurements were repeated after 6 weeks. MAIN OUTCOME MEASURE: Lung function. RESULTS: 44 children with a median age of 11.3 months (range 3.7-25.9) completed the study. Median sGaw improved from a z score of -3.6 to -1.2 (p<0.001) in the budesonide group and from -3.2 to -2.6 (p = 0.033) in the placebo group; between group difference p = 0.014. Improvement in sGaw was more pronounced in children with atopy (p = 0.017). Symptom-free days increased in both the budesonide and placebo groups with no difference between groups. CONCLUSION: Treatment with inhaled budesonide for 6 weeks improved sGaw in young children with chronic cough or wheeze and bronchial obstruction.

Effect of adenoidectomy on respiratory function: a randomised prospective study.

OBJECTIVE: Risk of childhood asthma is increased in children with recurrent otitis media. This may be associated with recurrent respiratory tract infections in these children, but the role of adenoidectomy, a frequent operation during childhood, is unknown. Therefore, the role of adenoidectomy in the development of atopy and respiratory function changes characteristic of asthma was evaluated. DESIGN: Randomised controlled study. SETTING: Tertiary care centre. PATIENTS: 166 children aged 12-48 months who had recurrent or persistent otitis media and who were followed-up for 3 years after randomisation. INTERVENTION: Randomisation to undergo insertion of tympanostomy tubes with or without adenoidectomy. MAIN OUTCOME MEASURES: The primary outcome measure was exercise-induced bronchoconstriction as evaluated by impulse oscillometry. The secondary outcome measures were bronchial inflammation as evaluated by exhaled nitric oxide and atopy as evaluated by skin prick tests. During the 3-year follow-up period otitis media episodes were documented in patient diaries. RESULTS: Adenoidectomy did not significantly influence baseline lung function, exercise-induced bronchoconstriction, exhaled nitric oxide concentration, the development of positive skin prick tests, or doctor-diagnosed asthma. Adenoidectomy did not significantly prevent otitis media. Recurrent otitis media (>or=4 episodes) during the first follow-up year was associated with an abnormal exercise-induced bronchoconstriction (OR 6.62, 95% CI 1.27 to 34) and an elevated exhaled nitric oxide concentration (OR 3.26, 95% CI 0.98 to 10.8) regardless of adenoidectomy. CONCLUSIONS: Adenoidectomy did not promote asthma or allergy. Recurrent respiratory tract infections during early childhood are associated with the risk of bronchial hyper-reactivity.

Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age.

BACKGROUND: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3(+) Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. METHODS: Immunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4-23 months of age, under investigation for airway disease. RESULTS: A well developed HLA-DR(+) network of APC was present in all samples, approximately 50% of the cells being CD68(+) macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR(+) cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a(+) dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3(+) Treg were located primarily within these isolated lymphoid follicles. CONCLUSION: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy.

Airway responsiveness: associated features in infants with recurrent respiratory symptoms.

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.

Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: A SOMA study.

Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting beta2-agonist with as-needed use of a beta2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled beta2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) > or =20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis Turbuhaler) 4.5 microg as needed (n = 47) or budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg as needed (n = 45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7- -0.7). In the budesonide/formoterol group, use of > or =4 inhalations x day(-1) of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a beta2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.

Reference values for respiratory system impedance by using impulse oscillometry in children aged 2-11 years.

The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample (n = 360) of children (age 2.1-11.1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90-160 cm) are presented.

Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values.

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Determinants of increased exhaled nitric oxide in patients with suspected asthma.

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.

Controlled trial of dexamethasone in neonatal chronic lung disease: an 8-year follow-up of cardiopulmonary function and growth.

AIM: To evaluate the long-term effects of postnatal dexamethasone treatment in high-risk infants of very low birthweight. METHODS: The study included 16 children aged 7.8 to 9.2 y who had been born very prematurely at gestational ages of 24-29 wk and with birthweights of < 1500 g and who had participated in a randomized study of dexamethasone or placebo treatment in ventilator-dependent infants at 10 d of age. Flow-volume spirometry, impulse oscillometry, skin-prick tests and Doppler echocardiography were carried out at school age, and respiratory morbidity and overall neurological outcome evaluated. Controls were 18 non-atopic children born at term, tested for lung function. RESULTS: No significant differences were found in respiratory morbidity at school age between the dexamethasone (n = 8) and placebo (n = 8) groups. Six of the 16 children had moderate to severe neurosensory impairments, but all were able to walk without support and attended primary school. In prematurely born children, standardized height was significantly less than that in controls, but between the two study groups, no significant differences existed in somatic growth. Atopy was uncommon: skin-prick tests were positive in only one child in the placebo group. In the dexamethasone group, forced vital capacity adjusted to height was significantly higher than that in the placebo group, but impairment of basic lung function and bronchial obstruction was evident in both study groups. No hypertrophic cardiomyopathy was apparent, and non-invasive measurements of pulmonary arterial pressure did not reveal any significant difference between the study groups. CONCLUSION: In very low-birthweight children, high respiratory morbidity and neurological impairment continued until school age. Neonatal dexamethasone treatment at school age was not associated with any detectable adverse effects on somatic growth, or pulmonary or cardiac function.

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

Determinants of respiratory system input impedance and bronchodilator response in healthy Finnish preschool children.

In order to study the determinants of respiratory system impedance and bronchodilator response in preschool children, a sample (n = 109) of healthy children (age 2.1-7.0 years) attending kindergarten was measured by using the impulse oscillometry. Their selection was based on a standardized questionnaire, negative skin prick test results and clinical examination, and sufficient cooperation. Triple measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance frequency (Fr) and the frequency dependence of resistance (dRrs/df) were performed, to determine individual mean values. Measurements were repeated after inhalation of 300 microg salbutamol (n = 89) or placebo (n = 19). At the baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive correlations with age, height and weight. However, logarithmic transformed height was the best independent variable for the regression equations of all the oscillometric variables. After inhalation of placebo, none of the oscillometric variables changed significantly. In the salbutamol group, the mean (SD) change in Rrs5 was -0.187 (0.124) kPa l(-1) s(-1) and -19.2 (10.2)%, corresponding to a lower reference limit of -36.9%. Both the within-test and between-test repeatabilities for the measurement of respiratory resistance were acceptable, for Rrs5 the coefficients of variation being 6.2 and 6.1%, respectively. As the overall success rate in our sample was high (89%), the forced oscillation technique seems to be a useful method in assessing respiratory function and bronchial lability in preschool children.

Acceptability, reproducibility, and sensitivity of forced expiratory volumes and peak expiratory flow during bronchial challenge testing in asthmatic children.

OBJECTIVES: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children. DESIGN: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined. PATIENTS: One hundred five children with newly diagnosed asthma, aged 5 to 10 years. RESULTS: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children. CONCLUSIONS: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction.

Disturbances in airflow dynamics and tracheal sounds during forced and quiet breathing in subjects with unilateral vocal fold paralysis.

Variable extra thoracic obstruction has been found in spirometric studies in subjects with unilateral vocal fold paralysis. The aim of the study was to further evaluate airflow dynamics in these subjects with body plethysmography and tracheal sound analysis. Ten patients with unilateral vocal fold paralysis without a history of chronic pulmonary diseases and 10 healthy control subjects were studied. Flow-volume spirometry, body plethysmography and tracheal sound analysis were performed within 1 day. The study shows that peak inspiratory flow (PIF) and specific airway conductance (SG(aw)) expressed as percentage of Finnish reference values were significantly lower and airway resistance (R(aw)) was higher among the patients than among the controls (P=0.004, P=0.026 and P=0.004, respectively). The patients had higher sound amplitude of both inspiratory and expiratory tracheal sounds than the controls [root mean square (RMS) values of the power spectra were 31.5 and 25 dB, P=0.006 in inspiration and 31.5 and 26 dB, P=0.013 in expiration, respectively]. Quartile frequencies (F25 and F50) and RMS of expiratory tracheal sounds had significant negative correlation with PIF (P=0.02, P<0.001, P=0.02, respectively) and forced inspiratory volume in 1 s (FIV(1)) (P=0.01, P<0.001, P=0.01, respectively). There was also an association between F50 and peak expiratory flow (PEF) (P=0.02). According to the present study, both quiet breathing and forced inspiration are disturbed in subjects with unilateral vocal fold paralysis. A close relationship between tracheal sounds and respiratory function tests exists.

Tracheal sounds and airflow dynamics in surgically treated unilateral vocal fold paralysis.

The aim of this study was to investigate the changes in tracheal sounds and airflow dynamics in patients who underwent surgical medialization of a unilaterally paralysed vocal fold. Ten adults with unilateral vocal fold paralysis but no history of pulmonary diseases were included. Vocal fold medialization was performed by an injection of autologous fascia into the paralysed vocal fold. Recording of tracheal sounds, flow-volume spirometry and body plethysmography were carried out before and 4-14 months after the operation. The mean number of inspiratory wheezes per respiratory cycle increased from 0.02 (range 0-0.10) to 0.42 (range 0-0.86) and the mean number of expiratory wheezes per respiratory cycle from 0.03 (range 0-0.20) to 0.36 (range 0-0.89). The increment was statistically significant (P=0.03 and P=0.04, respectively). The mean expiratory sound amplitude, in terms of root mean square (RMS), increased from 31.5 dB (range 24.0-38.0) to 34.9 dB (range 25-42) (P=0.03) and the average peak inspiratory flow (PIF) decreased from 4.63 l s-1 (range 2.84-7.51) to 4.03 l s-1 (range 2.27-6.68) (P=0.01). The results indicate that when the paralysed vocal fold is brought into midline by a surgical procedure, the prevalence of inspiratory and expiratory wheezes increases and sound intensity rises. According to this preliminary data tracheal sound analysis gives additional information for the assessment of the subtle changes in the larynx.

Lung function measured by the oscillometric method in prematurely born children with chronic lung disease.

Premature birth is related to a chronic respiratory morbidity, which may persist until school-age. In these children, the forced oscillation technique would be suitable for evaluation of lung function even at preschool age, since it requires only minimal patient cooperation. In order to investigate the oscillometric findings related to premature birth, using the oscillation technique and conventional lung function methods 49 school-aged children born prematurely with (n=15) or without (n=34) chronic lung disease (CLD), and 18 healthy children born at full term were studied. Children with CLD had higher respiratory resistance (Rrs,5) and lower reactance (Xrs,5) than prematurely born children without CLD or healthy controls. Both Rrs,5 (r=-0.55, p<0.0001) and Xrs,5 (r=0.76, p<0.0001) were significantly associated with forced expiratory volume in one second (FEV1), the agreement with spirometry being better in Xrs,5 than in Rrs,5 (p=0.02). Rrs,5 was significantly related to airway resistance (Raw) measured by body plethysmography (r=0.63, p<0.0001), but underestimated resistance at high values of Raw. There was no significant relationship between the pulmonary diffusing capacity and the oscillometric findings. Compared to conventional methods, the oscillometric method yields concordant information on the severity of lung function deficit in children born prematurely, with or without chronic lung disease. In these children, the oscillometric findings are probably due to peripheral or more widespread airway obstruction. As conventional methods are not usually suitable for preschool children, oscillometry may serve as an alternative for early evaluation of chronic lung disease among children with premature birth in clinical or research settings.

Orthostatic increase of respiratory gas exchange in hyperventilation syndrome.

BACKGROUND: Hyperventilation syndrome (HVS) is a common disorder which is difficult to diagnose because of somatic symptoms and its episodic nature. In previous studies respiratory alkalosis in arterial blood was often found during orthostatic tests in patients with HVS. The purpose of this study was to assess these orthostatic changes by non-invasive pulmonary gas exchange measurements and to evaluate whether these responses discriminate patients with HVS from healthy subjects. METHODS: Respiratory gases were collected with a face mask and pulmonary gas exchange was measured after 10 minutes at rest and after eight minutes standing upright in 16 patients with HVS and 13 healthy control subjects. In patients with HVS arterial blood samples were also drawn at rest and in the standing position. RESULTS: At rest the variables of respiratory gas exchange did not differ significantly between the groups. As a response to standing, minute ventilation increased in both study groups but significantly more in the patients with HVS (mean difference 5.4 l/min (95% CI 1.1 to 9.6)). The changes in end tidal CO(2) fraction (FETCO(2)) and in ventilatory equivalents for oxygen (VE/VO(2)) and for CO(2) (VE/VCO(2)) during the orthostatic test were also significantly larger in patients with HVS than in healthy controls. During standing FETCO(2) was significantly lower (mean difference -1.1 kPa; 95% CI -1.5 to -0.6) and VE/VO(2) (mean difference 18.4; 95% CI 7.7 to 29.0) and VE/VCO(2) (mean difference 11.7; 95% CI 4.8 to 18.6) were significantly higher in HVS patients than in healthy controls. By using the cut off level of 4% for FETCO(2) the sensitivity and specificity of the test to discriminate HVS were 87% and 77%, respectively, and by using the cut off level of 37 for VE/VO(2) they were 93% and 100%, respectively. In the HVS patients arterial PCO(2) and FETCO(2) were closely correlated during the orthostatic test (r = 0.93, p<0.0001). CONCLUSIONS: As a response to change in body position from supine to standing, patients with HVS have an accentuated increase in ventilation which distinguishes them from healthy subjects. These findings suggest that non-invasive measurements of pulmonary gas exchange during orthostatic tests are useful in the clinical evaluation of patients with hyperventilation disorders.