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Many patients born prematurely who developed bronchopulmonary dysplasia (BPD) as neonates are now approaching adulthood. Adults with BPD are at increased risk for respiratory difficulties including respiratory and lung function disorders. Respiratory symptoms include wheezing, cough and dyspnoea. In adult BPD patients lung function is impaired, notably by bronchus obstruction, hyperreactivity and reduced diffusion capacity; exercise capacity is also diminished. The pathophysiology of BPD is not identical to that of asthma and standard treatment for asthma is therefore not effective. Premature infants are currently treated with surfactant therapy that results in less intensive artificial respiration and oxygen being required. The classical BPD clinical picture that results from tissue damage and scarring is therefore becoming less common but another new BPD picture is emerging. This is characterised by large irregularly formed sacculi and alveoli with septation only just beginning and poor vascularization. Patients with chronic respiratory symptoms who were born prematurely should therefore undergo comprehensive testing, including detailed lung function tests and exhaled nitric oxide levels.

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OBJECTIVE: To investigate the respiratory health of preterm infants with bronchopulmonary dysplasia (BPD) at preschool age and to determine whether lung function (measured by forced oscillation technique (FOT) and interruption technique (Rint) is affected by BPD in preterm infants compared with preterm infants without BPD. PARTICIPANTS: 3 to 5 years of age born preterm with BPD (N = 40, mean gestational age 28 weeks, mean birth weight 1051 g), and without BPD (N = 36, mean gestational age 29 weeks, mean birth weight 1179 g). OUTCOME VARIABLES: prevalence of symptoms determined by European Community Respiratory Health Survey and lung function measured by FOT and Rint. RESULTS: A large percentage of infants in both preterm groups reported respiratory symptoms during the last 12 months. Lung function measurements showed higher resonant frequency (Hz) in BPD compared with non-BPD (mean 26.8 vs 22.7, P < .001) and lower mean reactance X(4-24) (hPa.s/l)(-3.0 vs -1.9, P = .005). No differences were found in respiratory resistance between the groups, although the mean values of both groups were increased compared with reference values. CONCLUSION: Preterm birth affects respiratory health at 3 to 5 years of age. Children with BPD could be distinguished from children without BPD based on a higher resonant frequency and a lower mean reactance.

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Chronic lung disease of the neonate sometimes occurs as a residual condition following respiratory distress in preterm infants. Improvements in neonatal intensive care treatment will in future lead to a greater number of children surviving chronic lung disease and reaching adulthood. The symptoms of the disease are hypoxaemia, hypercapnia, tachypnoea, subcostal and intercostal retractions, fluid retention, a reduced exertion tolerance and hyperreactive airways. The treatment after the first weeks of life is symptomatic and consists of: providing supplemental oxygen via a nasal mask or cannula (0.1-1 l/min); rapid downward adjustment of oxygen therapy may lead to more complaints and poorer growth; a normal fluid therapy; if there is a tendency towards fluid retention, then diuretic therapy is indicated and in severe cases fluid restriction as well; in the case of bronchial hyperreactivity: inhaled corticosteroids (the lowest effective dose for a period of several months) and a trial treatment with beta-agonists; in the case of persistent complaints or functional limitations, lung function tests can distinguish obstructive and restrictive disorders; vaccinations according to the national programme; consider vaccinations against influenza (age: 6-12 months) and respiratory syncytial virus (age < 2 years).

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Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 microg ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E4 (U-LTE4) and 9alpha11beta prostaglandin F2 (U-9alpha11beta PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta2-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.

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This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma. Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12-18 yrs of age, FEV1 65-110% of predicted, on 500-2,000 microg inhaled steroids daily). FEV1 was reversible by 13.3-2.3% pred. After sputum induction, FEV1 was still increased by 9.0+/-2.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4-59.5)% squamous cells, 47.3 (6.8-84.0)% macrophages, 39.0 (4.6-84.8)% neutrophils, 4.8 (1.0-12.4)% lymphocytes, 0.4 (0-10.8)% eosinophils and 3.6 (0-23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03). In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with beta2-agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma.

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