bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of biphasic positive airway pressure in patients with chronic obstructive pulmonary disease
Authors: Katz-Papatheophilou E , Heindl W , Gelbmann H , Hollaus P , Neumann M
Published: October 2002

Biphasic positive airway pressure (BiPAP) is a ventilatory mode in which two pressure levels (higher (Phigh) and lower (Plow)) acting as continuous positive airway pressure (CPAP) alternate at preset time intervals. BiPAP combines pressure-controlled ventilation with unrestricted spontaneous breathing. BiPAP has not yet been evaluated in patients with chronic obstructive pulmonary disease (COPD). Therefore, the effects of BiPAP (15 cmH2O Phigh and 5 cmH2O Plow) pressure support (PS; 15 cmH2O and positive end-expiratory pressure (PEEP) 5 cmH2O) and CPAP (5 cmH2O) on respiratory mechanics in COPD patients were compared. Twenty-one COPD patients were supported in randomized order with BiPAP, PS and CPAP. Pressure-time product (PTP), work of breathing (WOB), change in oesophageal pressure (deltaPoes), mouth occlusion pressure (P0.1), intrinsic PEEP (PEEPi), tension time index (TTI), respiratory frequency, and tidal volume (VT) were measured. During BiPAP, the COPD patients showed a significantly higher PTP, WOB, deltaPoes, P0.1, TTI and PEEPi than during PS. Comparing the Plow phases of BiPAP and CPAP, the breaths during the Plow phases of BiPAP had a lower VT and a greater WOB and PTP due to a higher PEEPi than on CPAP alone. In conclusion, biphasic positive airway pressure carries the risk of increased work of breathing in spontaneously breathing chronic obstructive pulmonary disease patients. Pressure support is superior for reducing their respiratory muscle effort.
Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking
Authors: Miller M.R. , Sigsgaard T. , Omland O. , Pedersen O.F.
Published: October 2002

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR.

The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e.α175%F, α175%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1and α175%, and also by the method of log dose slopes (LDS).

Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20FEV1could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1was recorded in 1,725 (88%) subjects. From the prechallenge data, α175%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects.

The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.
Snoring detection during auto-nasal continuous positive airway pressure
Authors: Lofaso F. , Leroux K. , Quera-Salva M.A. , Mroue G. , D'Ortho M.P. , Isabey D. , Louis B.
Published: October 2002

A bench study using an artificial lung model was performed to evaluate the snoring detection sensitivity of six (commercially available) auto-nasal continuous positive airway pressure (NCPAP) devices.

Snoring was simulated by a loudspeaker connected to the lung model and abruptly activated during 1 s of each inspiratory period to induce pressure oscillation. The oscillation frequencies chosen were 30, 60, 90, and 120 Hz. For each frequency, the amplitude of the pressure oscillation produced by the loudspeaker was adjusted to find the threshold at which the auto-nCPAP devices detected snoring.

Differences in pressure-amplitude thresholds of up to three-fold were found across auto-nCPAP devices. A randomized clinical study to compare the effects of the least sensitive (Virtuoso LX; Respironics, Nantes, France) and one of the most sensitive, (Goodknight 418A; Malinckrodt, Nancy, France) devices, in two groups of six patients with obstructive sleep apnoea syndrome was then conducted. Goodknight 418A was more sensitive than Virtuoso LX for detecting snoring (mean±sd 92±11%versus50±39% respectively, p=0.03).

To conclude, striking differences exist between auto-nasal continuous positive airway pressure devices in sensitivity for detecting snoring.
Perinatal predictors of respiratory symptoms and lung function at a young adult age
Authors: Boezen H.M. , Vonk J.M. , van Aalderen W.M.C. , Brand P.L.P. , Gerritsen J. , Schouten J.P. , Boersma E.R.
Published: October 2002

A longitudinal cohort of 2,957 babies, born in 1975–1978, was used to investigate whether perinatal factors predict respiratory morbidity at a young adult age.

In 1997, the presence of asthmatic (wheeze, nocturnal dyspnoea) and bronchitic (cough, phlegm, dyspnoea grade 3) symptoms and the level of lung function was determined in this cohort. The independent association between smoking during pregnancy, being first-born, birth weight and respiratory symptoms and lung function at young adult age was investigated using multiple regression models, taking other potential risk factors into account.

Of 1,568 responders, 608 (39%, aged 18–22 yrs) had at least one respiratory symptom. The young adults who had a mother that smoked during pregnancy had a significantly lower level of lung function than their nonintra-uterine exposed peers (regression coefficient (B) (standard error): peak expiratory flow (PEF) −0.257 (0.131) L·s−1; forced expiratory flow when 25% of the forced vital capacity has been exhaled (FEF25) −0.290 (0.129) L·s−1), although they were not at increased risk of having respiratory symptoms. Young adults who were first-born had better levels of lung function (B (se): forced expiratory volume in one second (FEV1) 0.090 (0.042) L) and were less likely to have asthmatic symptoms (odds ratio (95% confidence interval): 0.58 (0.35–0.95)) than those not first-born. Low birth weight (FEV1−0.013 (0.004) L for a reduction of 100 g) was also predictive of reduced achieved levels of lung function at young adult age, independent of other potential risk factors,e.g.current smoking habits or familial predisposition.

This study adds to the knowledge of the role of perinatal factors, such as smoking during pregnancy, as important predictors of respiratory morbidity.
Effects of insulin-like growth factor on nitrogen balance during hypoxic exposure
Authors: Iioka Y. , Tatsumi K. , Sugito K. , Moriya T. , Kuriyama T.
Published: October 2002

Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied with hypoxaemia may induce net protein catabolism and hypoxaemia could be an important trigger of a systemic catabolic response. The aim of this study was to examine the anabolic effects of recombinant human insulin-like growth factor‐I (IGF‐I) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied with a decrease in dietary intake, the usual nitrogen intake was maintained in this study.

Sprague-Dawley rats were maintained by continuous infusion of solution for total parenteral nutrition for 6 days. The animals were then randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3 days of the experiment N and H rats were randomised to receive either IGF‐I or vehicle.

Exposure to hypoxia caused a decrease in body-weight gain accompanied by a negative nitrogen balance, which was mainly due to increased urinary nitrogen excretion. No effect of recombinant human IGF‐I treatment on body weight was observed during exposure to hypoxia, although nitrogen balance normalised.

The co-infusion of recombinant human insulin-like growth factor‐1 and total parenteral nutrition has a significant net anabolic effect, as demonstrated by nitrogen retention and reduction in urine protein excretion observed in rats. Insulin-like growth factor‐1 may help to ameliorate the protein catabolism observed under hypoxic conditions.
Inpatient resource utilisation in younger (2–5 yrs) and older (6–14 yrs) asthmatic children in Finland
Authors: Valovirta E. , Sazonov Kocevar V. , Kaila M. , Kajosaari M. , Koivikko A. , Korhonen K. , Linna O. , Mäkelä M. , Remes K. , Ben-Joseph R.H.
Published: October 2002

Asthma is the most common chronic disorder among Finnish children, however, the economic burden of paediatric asthma in Finland has not yet been comprehensively evaluated. The objective of this study was to compare inpatient resource utilisation between younger (2–5 yrs) and older children (6–14 yrs) with asthma in Finland.

A national database of inpatient resource utilisation was applied to determine use of hospital services among children with asthma in 1999. Regional estimates of charges were combined with hospitalisation episodes to determine total inpatient cost.

The results indicate that younger asthmatic children consume 3‐times more inpatient resources per capita. Incidence of first admissions because of asthma was 3‐times higher in younger children. Hospitalisation and rehospitalisation rates were also 3‐ and 4‐times higher, respectively.

The total annual inpatient cost of asthma in children aged 2–5 and 6–14 yrs was E 1.98 million with each group accounting for E 1.12 million and E 0.86 million, respectively. Regional and age-related differences in hospitalisation rates and costs were likely related to variable clinical practice on the primary level, difficulties with diagnosis and compliance among younger children.
Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden
Authors: Boffetta P. , Ye W. , Boman G. , Nyrén O.
Published: October 2002

It has been suggested that asthma increases the risk of lung cancer in males but not in females. However, previous studies may suffer from report bias and are based on a small numbers of cases.

The objective of the present study was to assess the incidence of lung cancer in males and females using a nationwide Swedish cohort of asthma patients.

Patients (n=92,986) aged ≥20 yrs with a hospital-discharge diagnosis of asthma and who were alive and free from malignancy 1 yr after first hospitalization were followed-up, for incidence of lung cancer during the period 1965–1994 (average duration of follow-up, 8.5 yrs). Their incidence of lung cancer was compared with that of the national population.

The authors observed 713 lung cancers (standardized incidence ratio (SIR) 1.58, 95% confidence interval (CI) 1.47–1.70). The SIR was 1.51 in males (95% CI 1.38–1.65, 492 cases) and 1.78 in females (95% CI 1.55–2.03, 221 cases). The SIR decreased with duration of follow-up and increased with calendar period and age at first hospitalization. The risk of lung cancer was higher for squamous cell and small cell carcinoma than for adenocarcinoma, and it was higher in patients with other diseases as the main diagnosis and in patients hospitalized in departments other than internal and respiratory medicine.

It was confirmed that asthma patients are at increased risk of lung cancer, but there is no heterogeneity in risk between the sexes. Several indirect arguments point towards a noncausal explanation of these findings; in particular, confounding by tobacco smoking is a plausible explanation.
Enhanced IL‐4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy
Authors: Pala P. , Bjarnason R. , Sigurbergsson F. , Metcalfe C. , Sigurs N. , Openshaw P.J.M.
Published: October 2002

Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a “wheezy” predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)‐4 and interferon (IFN)‐γ responses to a panel of antigens were studied in a well-characterised cohort of 7–8‐yr-old children with a history of severe RSV bronchiolitis in infancy.

Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulatedin vitrowith RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN‐γ and IL‐4 production were measured.

IL‐4 producing T‐cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN‐γ response to RSV) were equally strong in exbronchiolitics and controls.

Respiratory syncytial virus infection primes memory T‐cells that make interferon‐γ, but virus and aeroallergen-specific and interleukin‐4 producing T‐cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin‐4‐rich environment, in which airborne allergens are first encountered.
Exhaled nitric oxide and bronchial responsiveness in healthy subjects exposed to organic dust
Authors: Sundblad B-;M. , Larsson B-;M. , Palmberg L. , Larsson K.
Published: October 2002

Inhalation of organic dust from swine houses causes an intense inflammatory reaction in the respiratory tract, and increased bronchial responsiveness to methacholine in healthy subjects. The aims of the present study were to investigate whether exhaled nitric oxide (NO) is a marker of the inflammation caused by exposure to organic dust (swine dust), whether there is a relationship between an increase in exhaled NO and bronchial responsiveness, and also whether wearing a half-mask influences the airway reaction (assessed by exhaled NO) and the increased bronchial responsiveness.

Thirty-three healthy nonatopic, nonsmoking subjects were exposed during 3 h of light work in a swine confinement building. Eleven of the subjects were wearing a half-mask and 22 were unprotected. Lung function, bronchial responsiveness and exhaled NO were measured before and after exposure.

The provocative concentration causing a 20% fall in forced expiratory volume in one second fell by 2.7 (2.1–4.1) (median (25th–75th percentiles)) doubling concentration steps in subjects without a half-mask and by 1.5 (0.9–2.9) doubling concentration steps in subject wearing a mask. Exhaled NO increased from 7.5 (5.7–13.7) parts per billion (ppb) before to 13.4 (10.5–17.5) ppb after exposure in the unprotected group and was unaltered (8.3 (6.1–14.1) to 8.6 (6.6–14.6) ppb) in the group wearing a half-mask. There was no correlation between NO increase and provocative dose causing a 20% fall in the forced expiratory volume in one second decrease.

In conclusion, bronchial responsiveness and exhaled nitric oxide increased after exposure to a swine confinement facility. Half-mask abolished the increase in exhaled nitric oxide levels, but influenced the increase in bronchial responsiveness to a minor extent. These results indicate that these two outcome measures reflect different aspects of airway inflammation induced by exposure to a farming environment.
Bronchial reactions to the inhalation of high-dose tobramycin in cystic fibrosis
Authors: Nikolaizik W.H. , Trociewicz K. , Ratjen F.
Published: October 2002

It has been established that inhaled tobramycin has a positive effect on respiratory function inPseudomonas-aeruginosapositive patients with cystic fibrosis (CF). In a previous study the authors reported that low-dose tobramycin preparations containing the preservative phenol caused significant bronchial obstruction. Recently, high-dose tobramycin preparations with and without preservatives/phenol have become available.

To assess the airway response to these preparations flow/volume curves in 12 patients with CF (four males, eight females, mean age±sd=19.0±7.4 yrs) were measured. The tobramycin preparations: Nebicina® 2.0 mL (150 mg, containing the preservative phenol), Distobram® 3.0 mL (150 mg, containing preservatives), Tobi® 5.0 mL (300 mg), Tobi® 2.5 mL (150 mg), and Tobi® 5.0 mL, were used after bronchodilator application.

Immediately and/or 5 min after the tobramycin inhalations there was a significant fall in lung function with the different preparations. There was no significant difference between preparations with and without preservatives/phenol. The bronchial obstruction was comparable to that observed after the inhalation of low-dose tobramycin and after saline. After 10 min of inhalation, the lung function returned to baseline values. Most patients preferred the Tobi® 2.5 mL and disliked the Nebicina® preparation due to the unpleasant taste. Preceding treatment with bronchodilators prevented the decline in lung function.

Assessment of bronchial response at the first nebulisation of high-dose tobramycin and, in case of significant obstruction, β‐agonists in combination with the antibiotic inhalation are recommended.
Some factors affecting cerebral tissue saturation during obstructive sleep apnoea
Authors: Valipour A. , McGown A.D. , Makker H. , O'Sullivan C. , Spiro S.G.
Published: October 2002

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation.

Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7±27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimumSa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes.

Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1–73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43–6.85%. MeanSa,O2dips varied from 3.8–21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip wereSa,O2dip, minimumSa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant afterSa,O2was included in the regression equation.

Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.
Upregulation of nerve growth factor expression by human airway smooth muscle cells in inflammatory conditions
Authors: Freund V. , Pons F. , Joly V. , Mathieu E. , Martinet N. , Frossard N.
Published: October 2002

Recent studies have suggested that nerve growth factor (NGF) may play a role in inflammation and bronchial hyperresponsiveness in asthma. Neither the types of cells that produce NGF in the human airways nor the effect of inflammation on NGF expression are clear. The two-fold aim of the present study was to determine whether airway smooth muscle produces NGFin vitro, and, if so, whether the pro-inflammatory cytokine interleukin-1β (IL-1β) affects this expression.

Human airway smooth muscle cells in culture were incubated in the presence or absence of IL-1β. NGF production was measured by enzyme-linked immunosorbent assay. NGF messenger ribonucleic acid (mRNA) was measured using a specific real-time fluorescent polymerase chain reaction technique, and expressed in relation to glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA levels.

Human airway smooth muscle cellsin vitroexpressed NGF constitutively (21.4±7.8 pg·mL−1; 14.6±5.4 pg NGF complementary deoxyribonucleic acid (cDNA)·pg GAPDH cDNA−1(mean±sem)). Stimulation with IL–1β (0.1–30 U·mL−1) for 24 h induced a dose-dependent increase in NGF production (22.1 pg·mL−1at 10 U·mL−1; p<0.05). The IL-1β (10 U·mL−1)-induced increase in NGF expression was time-dependent. It was highest for NGF protein at 10 h (1.6-fold increase over control; p<0.001) and for NGF mRNA at 2.5 h (2.4-fold increase over control; p<0.05).

In conclusion, the present study clearly shows that the human airway smooth muscle cell is a source of nerve growth factor, the expression of which is upregulated in inflammatory conditions, mimickedin vitroby the addition of interleukin-1β.
Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: anin vitrostudy
Authors: Peinado V.I. , Santos S. , Ramírez J. , Roca J. , Rodriguez-Roisin R. , Barberà J.A.
Published: October 2002

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulusin vitroin COPD, and the role of endothelium-derived nitric oxide (NO) in this response.

The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO.

Compared with the other groups, HV was reduced in COPDH. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV.

In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.
Scientific rationale for inhaled combination therapy with long-acting β2-agonists and corticosteroids
Authors: Barnes P.J.
Published: October 2002

The addition of an inhaled long-acting β2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients and two fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are increasingly used as a convenient controller in patients with persistent asthma. There is a strong scientific rationale for the combination of these two drug classes.

ICS suppress the chronic inflammation of asthma and reduce airway hyperresponsiveness and this is achieved at low doses in most patients. LABA act on different aspects of the pathophysiology of asthma. In addition to their bronchodilator action, LABA also inhibit mast cell mediator release, plasma exudation and may reduce sensory nerve activation. Thus these two classes of drug address complementary aspects of the pathophysiology of asthma that neither drug class is able to achieve alone.

There are several positive interactions between LABA and ICS. Corticosteroids increase the expression of β2-receptors by increasing gene transcription. Experimentally this protects against the loss of β2-receptors in response to long-term exposure to β2-agonists. While this is unlikely to be important in bronchodilator responses to β2-agonists, in view of the large β-receptor reserve, it is probably important in preventing loss of β-agonist effects on the nonbronchodilator actions of LABA discussed earlier. β2-Agonists may potentiate the molecular mechanism of corticosteroid actions, with increased nuclear localization of glucocorticoid receptors and additive or sometimes synergistic suppression of inflammatory mediator release. Thus LABA and ICS may optimize each others beneficial actions in the airways, but the low systemic effects of these drugs do not result in any increase in adverse effects.

Long-acting β2-agonists corticosteroid inhaler therapy is therefore a logical advance and results in effective control of asthma in the majority of patients without significant adverse effects. This simplified approach to long-term asthma therapy has a strong scientific rationale.
Evidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Authors: Louis R.E. , Cataldo D. , Buckley M.G. , Sele J. , Henket M. , Lau L.C. , Bartsch P. , Walls A.F. , Djukanovic R.
Published: October 2002

Although asthma has been viewed mainly as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in severe asthma and sputum eosinophilia in some COPD patients.

In an attempt to further characterise these two syndromes according to pathology, the current authors have conducted a study of induced sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy individuals. Sputum was analysed for cytology and levels of eosinophil cationic protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule‐1.

The COPD subjects differed from the asthmatics as they had higher sputum neutrophil and lower columnar epithelial cell counts, but there were no differences in any soluble marker studied. When compared to control subjects, both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels. In a subset of COPD subjects with sputum eosinophilia (>3% of total cells), significantly increased levels of tryptase were detected.

In conclusion, although chronic obstructive pulmonary disease is a more neutrophilic disease than asthma, the two diseases are difficult to distinguish on the basis of sputum levels of the soluble markers traditionally associated with asthma. However, a subset of patients with chronic obstructive pulmonary disease with airway eosinophilia and mast-cell activation might represent a distinct pathological phenotype.
Measurement of exhaled nitric oxide in children, 2001
Authors:   Members of the Task Force:, Baraldi E. , de Jongste J.C. , Gaston B. , Alving K. , Barnes P.J. , Bisgaard H. , Bush A. , Gaultier C. , Grasemann H. , Hunt J.F. , Kissoon N. , Piacentini G.L. , Ratjen F. , Silkoff P. , Stick S.
Published: October 2002

Measurement of fractional exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights in to the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques will facilitate the use of this new measurement in paediatric respiratory medicine; this Task Force was set up for this purpose. Methodologies, for use in all age groups, are already available and there are abundant questions relating to interpretation and application of fractional exhaled nitric oxide waiting to be addressed. Noninvasiveness and instantaneous results potentially make it a suitable monitoring instrument for use in children. Exhaled nitric oxide measurement has definitely found its way into clinical research in paediatric respiratory medicine. Evidence for clinically-useful applications is accumulating, and the merits of this new technique must now be demonstrated in larger studies, using standardised methodology in an appropriate setting.
Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled study
Authors: Eaton T. , Garrett J.E. , Young P. , Fergusson W. , Kolbe J. , Rudkin S. , Whyte K.
Published: October 2002

It is unknown whether acute response to ambulatory oxygen (O2) predicts longer term improvement in health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) patients.

The aims of this study were 1) to assess the short-term clinical impact, as determined by HRQL, of ambulatory O2in a 12-week, double-blind, randomised crossover study of O2(versuscylinder compressed air) of dyspnoeic but not chronically hypoxic COPD patients with exertional desaturation ≤88% (n=41), and 2) to determine whether either baseline characteristics or acute response to O2predicts short-term (12 weeks) response. Primary outcome measures were Chronic Respiratory Questionnaire (CRQ), Hospital Anxiety and Depression scale and the short form (SF)-36.

Improvements were seen in all domains of the CRQ for cylinder O2compared with cylinder air. Significant improvements were also noted in anxiety and depression and in certain domains of the SF-36. There were 28 (68%) acute responders to cylinder O2(defined as increase in 6‐min walk ≥54 m or decrease in post-Borg dyspnoea ≥1) and 23 (56%) short-term responders (defined as clinically significant improvement in CRQ). However, acute and short-term responses were not correlated with no predictors of short-term response identified. At study completion, 14 (41%) of acute or short-term responders did not want to continue therapy, with 11 citing poor acceptability or tolerability.

Short-term ambulatory oxygen is associated with significant improvements in health-related quality of life. These benefits cannot be predicted by baseline characteristics or acute response. Despite acute or short-term response, a substantial proportion of patients declined ambulatory oxygen.
The public health relevance of air pollution abatement
Authors: Künzli N.
Published: October 2002

Assuming a causal relationship between current levels of air pollution and morbidity/mortality, it is crucial to estimate the public health relevance of the problem. The derivation of air pollution attributable cases faces inherent uncertainties and requires influential assumptions. Based on the results of the trinational impact assessment study of Austria, France, and Switzerland, where prudent estimates of the air pollution attributable cases (mortality, chronic bronchitis incidence, hospital admissions, acute bronchitis among children, restricted activity days, asthma attacks) have been made, influential uncertainties are quantified in this review.

The public health impact of smoking, environmental tobacco smoke, and air pollution on the prevalence of chronic cough/phlegm are outlined. Despite all methodological caveats, impact assessment studies clearly suggest that public health largely benefits from better air quality. The studies are selective underestimates as they are strongly driven by mortality, but do not include full quantification of the impact on morbidity and their consequences on quality of life among the diseased and the caregivers.

Air pollution abatement strategies are usually political in nature, targeting at policies, regulation and technology in mobile or stationary sources rather than at individuals. It is of note that key clean air strategies converge into abatement of climate change. In general, energy consumption is very closely related to both air pollution and greenhouse gases. The dominant causes of both problems are the excessive and inefficient combustion of fossil fuel. Thus, for many policy options, the benefit of air pollution abatement will go far beyond what prudent health-impact assessments may derive. From a climate change and air pollution perspective, improved energy efficiency and a strong and decisive departure from the “fossil fuel” combustion society is a science-based must. Health professionals must raise their voices in the political decision process to give strong support for clean air policies, both on a national and international level.
Biochemical markers of cerebrovascular injury in sleep apnoea syndrome
Authors: Jordan W. , Hagedohm J. , Wiltfang J. , Laier-Groeneveld G. , Tumani H. , Rodenbeck A. , Rüther E. , Hajak G.
Published: October 2002

Sleep apnoea syndrome (SAS) is a known risk factor for vascular diseases and stroke. Structural brain damage, manifesting as an overt neurological deficit or more subtly as cognitive dysfunction, is a frequent symptom in SAS. The presence of a biochemical marker of cerebral injury would be of great benefit in SAS to screen for even small brain damage and to monitor efficiacy of therapy.

Therefore, in 10 patients with mild SAS (age 50.8±9.9 yrs, respiratory disturbance index (RDI) 18±3.6, lowest arterial oxygen saturation (minSa,O2) 80.5±4.06%) and nine patients with severe SAS (age 50.3±11.5 yrs, RDI 75.4±21.7, minSa,O256.56±14.58%), serum concentrations of neuron-specific enolase (NSE), S‐100β protein, and β‐trace were measured just before and after sleep using commercially available assays.

Only serum levels in the normal range could be found, independent of when the blood was taken or the degree of SAS.

Structural cerebral injury caused by sleep apnoea syndrome in patients without neurological symptoms or previous cerebrovascular events may be too small to produce a measurable increase in S‐100β, neuron‐specific enolase and β‐trace serum concentrations or subclinical cerebral damage may be outside the lower detection limits of the analytical methods which were used. There is a need for biochemical markers and more sensitive methods for detecting small cerebral injury in sleep apnoea syndrome.
Association of asthma and total IgE levels with human leucocyte antigen-DR in patients with grass allergy
Authors: Woszczek G. , Kowalski M.L. , Borowiec M.
Published: October 2002

Exposure to grass pollens during the pollen season, reveals in sensitive patients symptoms of allergic rhinitis, conjunctivitis and/or bronchial asthma. It is not well understood why, in some patients, only symptoms of rhinitis occur while in others similar exposure causes symptoms of asthma and rhinitis.

An association study is reported here, where the possible contribution of human leucocyte antigen (HLA)-DR gene polymorphisms to differential phenotypic expression of symptoms in patients with grass-pollen allergy was determined. HLA-DR genotyping was performed by the polymerase chain reaction with the sequence-specific primers method in 82 patients with symptoms of seasonal allergic rhinitis and/or bronchial asthma and 52 healthy nonatopic control subjects.

A significant association was found between HLA-DRB1*02, B5* haplotype and asthma phenotype in patients with grass-pollen allergy when compared to patients with rhinitis only. Significantly higher total serum immunoglobulin E levels were observed in patients with HLA-DRB1*01 alleles in comparison to patients without these alleles.

The data in this study suggest that human leucocyte antigen-DR locus, or other genes in linkage disequilibrium, may play an important role in asthma phenotype expression in patients with grass-pollen allergy as well as in determining total immunoglobulin E levels in these patients.
Effects of tracheotomy on respiratory mechanics in spontaneously breathing patients
Authors: Moscovici da Cruz V. , Demarzo S.E. , Sobrinho J.B.B. , Amato M.B.P. , Kowalski L.P. , Deheinzelin D.
Published: October 2002

Tracheotomy is a method of intubating the trachea, which is employed in several clinical settings, including the treatment of head and neck neoplasms. Tracheotomy is believed to facilitate weaning through changes in respiratory mechanics. Existing information concerning functional changes associated with tracheotomy are limited to comparisons with orotracheal intubation.

In this study, respiratory mechanics were monitored in seven spontaneously breathing patients, before and after an elective tracheotomy was performed for surgical treatment of cancer. Campbell diagrams were constructed by plotting pressure, obtained with an oesophageal balloon catheter, against volume, obtained from a pneumotachograph placed at the airway opening. Work of breathing was calculated as the internal area of the Campbell diagram and was partitioned into its elastic and inspiratory and expiratory resistive components. Oesophageal pressure was also used to quantify intrinsic positive end-expiratory pressure (PEEPi) and the pressure-time product (PTP), which is considered to be proportional to the oxygen cost of breathing. PTP was divided into its resistive and elastic components.

Inspiratory resistive work, PEEPi, inspiratory PTP, as well as its resistive and elastic components were significantly reduced by tracheotomy.

Tracheotomy significantly reduces work of breathing and pressure-time product in spontaneously breathing patients.
Genetic and environmental influence on asthma: a population-based study of 11,688 Danish twin pairs
Authors: Skadhauge LR , Christensen K , Kyvik KO , Sigsgaard T
Published: October 2002

The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from the Danish Twin Register. The cumulative incidence of asthma was 6.2% in the pooled sample. The data showed a decreasing cumulative incidence with age for males, but no sex or zygosity difference was observed. Substantially higher concordance rates, odds ratios and correlations for asthma were estimated in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age-dependency in the magnitude of genetic effects was observed. The biometric analysis emphasized a major influence of genetic factors in the aetiology of asthma. However, a substantial part of the variation in liability to asthma is due to the impact of environmental factors specific to the individual. There is no evidence for a substantial impact of genetic dominance or the shared environment.
Lung function in school-aged asthmatic children with inhaled cromoglycate, nedocromil and corticosteroid therapy
Authors: Korhonen K , Korppi M , Remes ST , Reijonen TM , Remes K
Published: October 2002

Two-thirds of the children with asthma in our area use cromones and only one-third steroids as the maintenance therapy. This study aimed to evaluate our treatment policy based on the international consensus. Peak expiratory flow (PEF), dynamic spirometry and bronchodilation test results were therefore collected in 195 school-aged patients who visited our outpatient clinic in 1995. Sixty-four children (33%) used cromoglycate, 86 (44%) nedocromil and 45 (23%) inhaled steroids. Twenty-five (12%) needed combination therapy, mainly with salmeterol. Lung function results were good, and there were no significant differences between the therapeutic groups irrespective of whether pre- or postbronchodilator values were considered. PEF was decreased in eight (4%), forced expiratory volume in one second (FEVI) in four (2%) and maximum mid-expiratory flow (MMEF) in 33 (17%) patients. At least one result was decreased in 39 (20%) cases, in most cases (77%) MMEF alone. Significant rises after salbutamol inhalations were observed in 17 (9%) in PEF, in two (1%) in FEV1 and 20 (10%) in MMEF values. Thus, the bronchodilation test was positive in 33 (17%) cases, and in 22 (11%) cases it was the only sign of bronchial obstruction. Over 70% of the children with asthma can be treated with cromones by a stepwise treatment modality. Inhaled steroids can be restricted to those not controllable by cromones. Lung function tests, including postbronchodilator values, should be part of the follow-up of continuous maintenance medication for asthma.
Seasonality, but not prevalence of sudden infant death syndrome varies by region in mainland Britain
Authors: Douglas AS , Helms PJ , Jolliffe IT
Published: October 2002

This study aimed to investigate whether seasonal variation in day length contributed to winter/summer variation in sudden infant death syndrome (SIDS) at different latitudes in mainland Britain. Over 11 yrs 13,973 deaths were studied. Using appropriate analytic techniques a sine curve was fitted to monthly rates with the amplitude indicating magnitude of seasonal change. The rate of SIDS per 1,000 live births was the same (1.73) in the north as in the south. The amplitude was a quarter less in the north (41.3%) than in the south (54.2%) (p<0.001). While annual rates did not differ, the within year distribution did. The findings for seasonality of SIDS births were similar (amplitudes: north 213%, south 32.3%). Correlations were made between SIDS amplitude and individual environmental factors, particularly temperature and day length. These complex issues, while reported briefly, do not allow firm conclusions. In the north the winter day length is shorter, sunshine hours are less and temperature is lower, but the winter increment in SIDS is less. The extent of seasonal variation of sudden infant death syndrome is greater in the south as compared with the colder, darker north but this has no effect on sudden infant death syndrome rates. Changing photoperiod by latitude, amongst other environmental influences, may hold clues to the aetiology of sudden infant death syndrome.
Arousal in patients with gastro-oesophageal reflux and sleep apnoea
Authors: Penzel T , Becker HF , Brandenburg U , Labunski T , Pankow W , Peter JH
Published: October 2002

Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of <4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of <4 during total sleep time (p<0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients.
Nocturnal blood pressure during apnoeic and ventilatory periods in patients with obstructive sleep apnoea
Authors: Tun Y , Okabe S , Hida W , Kurosawa H , Tabata M , Kikuchi Y , Shirato K
Published: October 2002

The exact nature of asleep blood pressure in relation to awake blood pressure is still unclear in patients with obstructive sleep apnoea. This study aimed: 1) to investigate the asleep blood pressure in both apnoeic and ventilatory periods; 2) to determine the diurnal and nocturnal factors correlated with the changes in blood pressure from apnoea to ventilatory periods during sleep. Thirty-two patients, newly diagnosed as moderate to severe obstructive sleep apnoea with a standard nocturnal polysomnography, were enrolled. The blood pressure was monitored by using the noninvasive continuous monitoring method during polysomnographic study. The mean blood pressures in ventilatory periods during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were 117.5+/-17.9 mm Hg and 128.8+/-21.9 mm Hg, and those in apnoea periods were 94.5+/-15.4 mm Hg and 102.7+/-19.0 mm Hg. The average blood pressure during NREM sleep (103.0+/-16.1 mm Hg) was higher than the awake blood pressure (97.0+/-15.7 mm Hg). The blood pressure during REM sleep was greater than that during NREM sleep. The changes in the nocturnal blood pressure from apnoea to ventilatory periods were inversely correlated with the age and nocturnal mean nadir saturation. In conclusion, patients with obstructive sleep apnoea have higher asleep blood pressure than awake blood pressure.
Protruding the tongue improves posterior rhinomanometry in obstructive sleep apnoea syndrome
Authors: Coste A , Lofaso F , d'Ortho MP , Louis B , Dahan E , Peynegre R , Harf A
Published: October 2002

In posterior rhinomanometry (PRM), oropharyngeal pressure is measured using a tube placed between the tongue and the hard palate. For valid results the patient must position the tongue and soft palate so that both the oropharynx and nasopharynx remain open. A high rate of failure of conventional PRM has been reported in normal individuals. In patients with obstructive sleep apnoea syndrome (OSAS), upper airway abnormalities may further increase the failure rate. This study proposes a modification of the technique in which protrusion of the tongue enhances pressure transmission between the nasopharynx and the mouth. In eight normal subjects, resistance was similar when measured by both methods. Of 24 OSAS patients, conventional PRM was unsuccessful in 11. In the remaining 13 patients, a significant correlation between the two methods was found, but resistance was lower by "tongue-out" than by conventional PRM, consistent with a decrease, during tongue protrusion, in retropalatal resistance, which is a component of the "nasal" resistance measured by PRM. In 26 OSAS patients, unilateral nasal resistance values measured by "tongue-out" PRM were similar to those measured by anterior rhinomanometry. When the "tongue-out" method was used routinely in 541 snorers, failure rates were 1.1% in the 272 non-OSAS patients and 3.7% in the 269 OSAS patients. These results indicate that posterior rhinomanometry with tongue protrusion is a highly effective tool for measuring nasal resistance in snorers.
Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry: a randomised study
Authors: Neder JA , Nery LE , Castelo A , Andreoni S , Lerario MC , Sachs A , Silva AC , Whipp BJ
Published: October 2002

All of the most widely-cited studies for the prediction of maximum exercise responses have utilized either volunteers or referred subjects. Therefore, selection bias, with overestimation of the reference values, is a likely consequence. In order to establish a set of predictive equations for the gas exchange, ventilatory and cardiovascular responses to maximum ramp-incremental cycle ergometry, this study prospectively evaluated 120 sedentary individuals (60 males, 60 females, aged 20-80), randomly-selected from >8,000 subjects. Regular physical activity pattern by questionnaire, body composition by anthropometry and dual energy X-ray absorptiometry (n = 75) and knee strength by isokinetic dynamometry were also assessed. Previously reported equations typically overestimated the subjects' peak oxygen uptake (p<0.05). Prediction linear equations for the main variables of clinical interest were established by backward stepwise regression analysis including: sex, age, knee extensor peak torque, bone-free lean leg mass, total and lean body mass, height, and physical activity scores. Reference intervals (95% confidence limits) were calculated: some of these values differed markedly from those formerly recommended. The results therefore might provide a more appropriate frame of reference for interpretation of the responses to symptom-limited ramp incremental cycle ergometry in sedentary subjects; i.e. those usually referred for clinical cardiopulmonary exercise tests.