Recurrent illness involving wheezing during the first years of life is transient in most children. The role of bronchial hyperresponsiveness as a factor influencing the persistence of wheezing from infancy to school age remains unknown. In a prospective study we investigated whether infants who wheezed and subsequently developed persistent asthma differed from infants who wheezed and later became asymptomatic either in the initial degree of bronchial hyperresponsiveness or in the persistence of bronchial hyperresponsiveness with age. One hundred and twenty-nine infants with three or more wheezing episodes before 2 yr of age were followed during 4 yr with a clinical evaluation and a methacholine challenge performed every 6 mo until the child was 4 yr old and once per year thereafter. The clinical score significantly improved with time in most children. The proportion of children with persistent wheezing after 2 and 4 yr of follow-up was only 31% and 20%, respectively. Persistent wheezers had significantly lower VmaxFRC values at initial evaluation and higher SRaw values at the end of follow-up than infants who became asymptomatic. We used transcutaneous oxygen tension (PtcO(2)) to measure the response to methacholine. No significant difference in PD(15) PtcO(2) between groups with subsequently different clinical progression was observed at initial evaluation. Bronchial hyperresponsiveness persisted 4 yr later in all children but children with persistent wheezing showed significantly lower PD(15) PtcO(2) values than children who became asymptomatic, as early as 30 mo of age. However, an acceptable early PD(15) PtcO(2) cut-off point predictive for subsequent clinical progression could not be identified. The level of bronchial hyperresponsiveness in infants who wheezed was not predictive of the persistence of asthma 4 yr later.
The effect of whole lung irradiation on lung function was investigated in 48 children treated for Wilm's tumour with pulmonary metastases. Lung function tests were performed before irradiation and were repeated annually for as long as possible, the length of follow-up varying from two to 17 years. A reduction in both lung volume and in dynamic compliance was clearly observed. In some patients these changes occurred in the early post-irradiation months, but in most the decrease observed progressed over longer periods of time. Static pressure volume curves, bloodgases, and carbon monoxide transfer were normal. These findings make it unlikely that postirradiation pulmonary fibrosis was involved. Another explanation for the decreased lung volume and dynamic compliance might be failure of alveolar multiplication. Muscular injury is unlikely as the patients were able to produce normal transthoracic pressures. A failure of chest wall growth is also possible and would explain the progressive restrictive impairment but not the early lung function changes. It is suggested that the early effects detected in some patients were the result of lung injury and that later effects resulted from impaired chest wall growth.Although the effects of pulmonary irradiation on lung function have been extensively investigated in adults, reports on the effects on respiratory function of whole lung irradiation are relatively few and there have been no reports of detailed, repeated lung function tests after this type of irradiation.In contrast to adults, young children are in a period of rapid lung and skeletal growth and the effect of pulmonary irradiation might be a failure of alveolar development resulting from impaired cellular proliferation, thus decreasing the number of alveoli. The aim of this study was to detect the shortand long-term pulmonary function changes in young children who received whole lung irradiation at doses which were therapeutically efficient but close to tolerance and we have tried to characterise the physiopathological mechanisms of the changes observed. Actinomycin D which enhances the effects of irradiation, was administered consecutively.1
Background: Sublingual immunotherapy (SLIT) has been demonstrated to be a viable alternative to injection immunotherapy. Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated. The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients. Methods: Sixty-four patients (age range 5–46 years) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind, placebo-controlled trial of SLIT. Sixty-three patients were randomized to four groups and evaluated at the end of the study. One group received placebo (n = 16) and the other three groups (n = 47) received five grass pollen extracts according to three different induction regimens: regimen 1 starting with 3 IR tablets (n = 15), regimen 2 starting with 10 IR (n = 16) and regimen 3 starting with 30 IR (n = 16). The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients. Adverse events were recorded on diary cards. Results: During induction phase, 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group (p < 0.05). The rate of adverse reactions was 33.3% (11.8–61.6) (95% CI) for regimen 1, 31.3% (11.0–58.7) for regimen 2, 43.8% (19.8–70.1) for regimen 3 and 12.5% (1.6–38.3) for placebo. Fifty-seven reactions were local reactions involving the oral region (54 SLIT, 3 placebo) and 13 were systemic reactions (all in the SLIT groups). 11/13 reactions were mild (gastrointestinal disorders, rhinoconjunctivitis), 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain. No urticaria, angioedema or life-threatening events were observed. Conclusions: These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT.
We assessed the ability of innovative lung function tests to detect bronchial obstruction induced by methacholine bronchial challenge. Fifty-five recurrently wheezy infants (mean age 16 +/- 5.2 months) free of respiratory symptoms underwent baseline lung function tests. Forty-two completed the methacholine challenge. Maximal flow at functional residual capacity (VmaxFRC) was obtained using the squeeze technique; compliance and resistance of the respiratory system (Crs, Rrs) was measured with the passive expiatory flow volume technique; tidal volume breathing patterns were analyzed from recordings of respiratory rate (RR), tidal volume (VT), and inspiratory time divided by total cycle of duration (Ti/Ttot). Expiratory tidal flow volume (V/VT) curves were described with multiple indices such as the ratio of expiratory time necessary to reach peak tidal expiratory flow (Fpet) to expiratory time (Tme/Te). Transcutaneous oxygen tension (PtCO2) was measured as an indicator of response to methacholine challenge. Of 42 infants 41 responded to methacholine by a change > or = 2 standard deviations from baseline values. The mean SD unit changes were 9.8 in PtCO2, 3.7 for VmaxFRC, 2.8 for Crs, 2.09 for Rrs, 3.1 for RR, 1.6 for Ti/Ttot, 2.2 for Tme/Te 3.9 for PFVt. We conclude that these noninvasive lung function tests, especially VmaxFRC and Fpet, can be used to detect minor or moderate airway obstruction. Further studies are needed to determine the value of the tests in assessing bronchial disease and effects of its treatment.
Wheezing during infancy has been linked to early loss of pulmonary function. We prospectively investigated the relation between bronchial hyperresponsiveness (BHR) and progressive impairment of pulmonary function in a cohort of asthmatic infants followed until age 9 years. We studied 129 infants who had had at least three episodes of wheezing. Physical examinations, baseline lung function tests and methacholine challenge tests were scheduled at ages 16 months and 5, 7 and 9 years. Eighty-three children completed follow-up. Twenty-four (29%) infants had wheezing that persisted at 9 years of age. Clinical outcome at age 9 years was significantly predicted by symptoms at 5 years of age and by parental atopy. Specific airway resistance (sRaw) was altered in persistent wheezers as early as 5 years of age, and did not change thereafter. Ninety-five per cent of the children still responded to methacholine at the end of follow-up. The degree of BHR at 9 years was significantly related to current clinical status, baseline lung function, and parental atopy. BHR at 16 months and 5 years of age did not predict persistent wheezing between 5 and 9 years of age, or the final degree of BHR, but it did predict altered lung function. Wheezing that persists from infancy to 9 years of age is associated with BHR and to impaired lung function. BHR itself is predictive of impaired lung function in children, strongly pointing to early airway remodeling in infantile asthma.
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