bluuebunny/crossref_metadata_2025 huggingface dataset:
Ageing does not influence the sleep-related decrease in the hypercapnic ventilatory response
Authors: Browne H.A.K. , Adams L. , Simonds A.K. , Morrell M.J.
Published: September 2008

In young people, a sleep-related reduction in the gain of the ventilatory chemoreflex feedback loop occurs; in the elderly, it has been reported that no sleep-related reduction occurs. A relatively high loop gain could contribute to periodic breathing and central sleep apnoea in the elderly. This study tested the hypothesis that ageing is associated with a reduction in the magnitude of the sleep-related decrease in the hypercapnic ventilatory response (HCVR).

The HCVR was measured using a steady state method, awake and asleep, in groups (n=10) of elderly (66–81 yrs) and young (23–35 yrs) nonapnoeics. Upper airway resistance was maintained close to wakefulness levels using continuous positive airway pressure (mean sleep-related increase in resistance: elderly 1.6±1.2 cmH2O·L·s−1, young 1.2±0.8 cmH2O·L·s−1).

The sleep-related decrease in the HCVR was similar in the elderly and young groups (elderly: wake 0.14±0.06 and sleep 0.06±0.02 L·min−1·kPa and young, wake 0.19±0.07 and sleep 0.10±0.04 L·min−1·kPa).

Ageingper sewas shown not to change the magnitude of the sleep-related decrease in hypercapnic ventilatory response. The authors speculate that age-related changes in the hypercapnic ventilatory response are unlikely to contribute to the increased prevalence of central sleep apnoea in the elderly.
Post-transplant bronchiolitis obliterans
Authors: Boehler A. , Estenne M.
Published: September 2008

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50–60% of patients who survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring after the third postoperative year.

This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.
Blood pressure responsiveness to obstructive events during sleep after chronic CPAP
Authors: Marrone O. , Salvaggio A. , Bonsignore M.R. , Insalaco G. , Bonsignore G.
Published: September 2008

The aim of this study was to investigate whether chronic continuous positive airway pressure (CPAP) affects blood pressure (BP) responsiveness to obstructive events occurring on the first night of CPAP withdrawal in obstructive sleep apnoea (OSA) after chronic treatment.

Thirteen male subjects with severe OSA underwent nocturnal polysomnography with beat­by­beat BP monitoring before treatment and after 4.9±3.4 months of home CPAP (mean daily use 5.1±1.7 h). Variations in oxyhaemoglobin saturation (ΔSa,O2), systolic (ΔPs), and diastolic (ΔPd) BP within nonrapid eye movement apnoeas and hypopnoeas were measured on a sample of pre­ and post­treatment events. In addition, a pretreatment sample was selected for ΔSa,O2to match post­treatment events.

The higher the mean ΔSa,O2was in the full pretreatment sample, the more ΔSa,O2, ΔPsand ΔPdwere attenuated after treatment. Mean ΔPsdecreased from 47.3±8.5 in the full pretreatment sample to 42.2±6.9 in the selected pretreatment sample, to 31.5±5.9 mmHg in the post­treatment sample. The post­treatment value differed significantly from both the pretreatment values. The corresponding values for mean ΔPdwere 27.0±3.5, 24.0±3.1 and 19.6±3.7 mmHg, with all values differing significantly from each other.

Chronic continuous positive airway pressure is followed by a decrease in apnoea/hypopnoea­related blood pressure swings, possibly secondary to both reduced severity of event­related hypoxaemia and decreased responsiveness to obstructive events secondary to chronic prevention of nocturnal intermittent hypoxaemia.
Chronic obstructive pulmonary disease: molecular and cellularmechanisms
Authors: Barnes P.J. , Shapiro S.D. , Pauwels R.A.
Published: September 2008

Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.

There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T‐lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.

The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
Agreement between written and video questions for comparing asthma symptoms in ISAAC
Authors: Crane J. , Mallol J. , Beasley R. , Stewart A. , Asher M.I.
Published: September 2008

Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma, rhinitis and eczema symptoms in children. In 99 centres from 40 countries, a total of just under 317,000 13–14-yr-old children also completed a video questionnaire, showing the symptoms and signs of asthma. This first video sequence has been compared to the ISAAC written question asking about current wheezing to explore variations in agreement and the contribution of each questionnaire to wheezing prevalence between centres, by region and language groups.

In general, responses to the video questionnaire gave a lower prevalence than the written questionnaire and responses were closely correlated. The overall proportion of agreement was high, mean 0.89, but unbalanced, with good negative agreement but poor positive agreement. Chance corrected agreement using Cohen's kappa coefficient, was generally low, with only 20 centres with kappa >0.4. The contribution of each questionnaire to wheezing prevalence also varied between centres and suggests that written questions about wheezing are variably understood and interpreted by 13–14 yr olds.

International comparisons of wheezing and its audiovisual presentation suggest that adolescents interpret a written question about wheezing differently from its audiovisual presentation and that this interpretation shows variation between centres. This relationship and the interpretation of both written and audiovisual presentation of symptoms requires further study in order to better predict asthma.
Hospital-acquired pneumonia: coverage and treatment adequacy of current guidelines
Authors: Ioanas M. , Cavalcanti M. , Ferrer M. , Valencia M. , Agusti C. , Puig de la Bellacasa J. , Torres A.
Published: September 2008

The American Thoracic Society (ATS) guideline for hospital-acquired pneumonia (HAP) released in 1996 and the Trouillet classification published in 1998 supply different rational foundations for the classification of patients with HAP and for the selection of initial antibiotic therapy. The aims of this study were to assess the level of bacterial coverage and to assess and validate the adequacy of antibiotic strategy of each of these classifications.

Intensive care unit-admitted patients (n=71) with suspicion of HAP were evaluated. The ATS and Trouillet classifications demonstrated an accuracy to predict the causative microorganism of 91% and 83%, respectively. The ATS and Trouillet antibiotic treatment recommendations were adequate in 79% and 80% of the patients, respectively. The microorganisms implicated in the treatment inadequacy of the ATS guideline werePseudomonas aeruginosa(n=3),Acinetobacter baumanii(n=1),Stenotrophomonas maltophilia(n=1) and methicillin-resistantStaphylococcus aureus(n=1).P. aeruginosawas implicated with Trouillet treatment inadequacy.

The current recommendations for empirical antibiotic treatment of hospital-acquired pneumonia (American Thoracic Society and Trouillet) showed a good ability to predict the involved pathogen. However, considering the resistance pattern of the isolated pathogens, both classifications demonstrated a rather lower treatment adequacy; the main reason was the failure to treat highly resistant strains.
Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD
Authors: Zühlke I.E. , Kanniess F. , Richter K. , Nielsen-Gode D. , Böhme S. , Jörres R.A. , Magnussen H.
Published: September 2008

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction.

A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42±4% predicted) received either 10 mg montelukast and 3 h later placeboviametered-dose inhaler (MDI) (M), or placebo and 3h later 200 µg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changesversusbaseline.

Compared to P, S caused significant bronchodilation in FEV1(7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1(1.5%). The saline-induced fall in FEV1was lower after M (−5.8%), compared with S (−10.3%) and P (−13.1%). FEV1(11.3%) and FIV1(7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1(8.5 min) and FIV1(15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1and/or inhaled corticosteroids.

Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.
Interleukin‐13 and ‐4 expression in the central airways of smokers with chronic bronchitis
Authors: Miotto D. , Ruggieri M.P. , Boschetto P. , Cavallesco G. , Papi A. , Bononi I. , Piola C. , Murer B. , Fabbri L.M. , Mapp C.E.
Published: September 2008

The aim of this study was to determine whether the T‐helper 2‐type cytokines interleukin (IL)‐13 and ‐4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB).

Surgical specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL‐4 and ‐13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL‐5+ and interferon (IFN)‐γ+ cells.

Compared to AS, the CB group had an increased number of IL‐13+ and ‐4+ cells in the bronchial submucosa, while the number of IL‐5+ and IFN‐γ+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL‐13 or ‐4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL‐13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL‐4+ cells were CD8+ and CD4+, respectively.

In conclusion, T‐helper‐2 and ‐1 protein expression is present in the central airways of smokers and interleukin‐4 and ‐13 could contribute to mucus hypersecretion in chronic bronchitis.
Clara cell protein as a biomarker for ozone-induced lung injury in humans
Authors: Blomberg A. , Mudway I. , Svensson M. , Hagenbjörk-Gustafsson A. , Thomasson L. , Helleday R. , Dumont X. , Forsberg B. , Nordberg G. , Bernard A.
Published: September 2008

Exposure to ozone (O3) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O3and the relationship between this marker of lung injury and early lung function decrements was investigated.

Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O3and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre-exposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure.

O3increased CC16 serum concentrations at 2 h (12.0±4.5versus8.4±3.1 µg·L−1) and 4 h postexposure (11.7±5.0versus7.9±2.6 µg·L−1) compared with air concentrations. Archived samples from O3studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1±2.6versus7.1±1.7 µg·L−1) with concentrations returning to baseline by 18 h (7.7±2.9versus6.6±1.7 µg·L−1). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes.

To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies.
In vivoassessment of lung inflammatory cell activity in patients with COPD and asthma
Authors: Jones H.A. , Marino P.S. , Shakur B.H. , Morrell N.W.
Published: September 2008

The involvement of inflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma is well established. This study aimed to quantify differences in inflammatory cell functionin situin these patients as compared to normal subjects.

Positron emission tomography was used to assess neutrophil activity (18F-fluorodeoxyglucose (18FDG)) and macrophage accumulation (11C-PK11195) in six patients with COPD, six chronic asthmatics and five age-matched normal control subjects.

18FDG uptake was greater in COPD than in normal subjects, with no increase in asthmatics. The mean slope of18FDG uptake, corrected for volume of distribution, was 4.0 min−1in COPD patients compared with 1.5 min−1in control subjects and 1.7 min−1in asthmatics. Mean11C-PK11195 uptake (plateau tissue:plasma) was higher in four of six COPD patients (10.8) and three of five asthmatics (11.8) than the maximum value in control subjects (6.2).

From this preliminary study the authors conclude that positron emission tomography may be useful to assess polymorphonuclear neutrophil and macrophage activityin vivoin chronic obstructive pulmonary disease and asthma, and may reveal differences in cell behaviour between the study groups. In addition, positron emission tomography may provide indices of disease activity for future therapeutic studies.
Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis
Authors: Gustafsson P.M. , Aurora P. , Lindblad A.
Published: September 2008

Many children with cystic fibrosis (CF), receiving modern, aggressive CF care, have normal spirometry results. This study aimed to see if homogeneity of ventilation distribution is impaired early in the course of CF lung disease, and if ventilation inhomogeneity is a more frequent finding than abnormal spirometry in children benefiting from modern CF care.

The study compared spirometry findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung clearance index (LCI)) from multiple-breath inert gas washout in 43 children with CF, aged 3–18 yrs, and 28 healthy children.

In total, 10/43 CF subjects (23%) had reduced forced expiratory volume in one second (FEV1) and 14/34 (41%) showed abnormal maximum expiratory flow at 25% of forced vital capacity (MEF25). In contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal in 22/33 CF subjects with normal FEV1,versus0/28 controls (p<0.001), and abnormal MR was found in 10/20 CF subjects with normal MEF25,versus0/22 controls (p<0.001). Nine of the 10 CF subjects with reduced FEV1and 12/14 with abnormal MEF25showed abnormal MR.

Inert gas washout discloses airway dysfunction in the majority of children with cystic fibrosis with normal lung function judged by spirometry. These findings suggest that multiple-breath inert gas washout is of greater value than spirometry in detecting early cystic fibrosis lung disease.
Bronchodilation test in COPD: effect of inspiratory manoeuvre preceding forced expiration
Authors: Santus P. , Pecchiari M. , Carlucci P. , Boveri B. , Di Marco F. , Castagna F. , Centanni S.
Published: September 2008

The effects of an inspiratory manoeuvre preceding forced expiration on functional tests performed under routine conditions before and after inhalation of a bronchodilator drug (salbutamol) were assessed on 150 consecutive chronic obstructive pulmonary disease outpatients. The patients performed forced vital capacity manoeuvres either immediately after a rapid inspiration (manoeuvre no. 1) or after a slow inspiration with a 4–6 s pause (manoeuvre no. 2).

Under baseline conditions, forced expiratory volume in one second (FEV1) values were 8% (% control) larger with manoeuvre no. 1 than no. 2. FEV1values increased with salbutamol administration by ∼8% and were, on average, still 7% larger with manoeuvre no. 1 than no. 2. The incidence of reversibility, assessed according to American Thoracic Society criteria, was 76% when manoeuvre no. 2 was selected to represent baseline conditions and manoeuvre no. 1 was chosen to represent the effects of bronchodilator administration, whereas the lowest incidence (2%) was found when manoeuvre no. 1 was selected to represent baseline conditions and manoeuvre no. 2 was chosen to represent the effects of bronchodilator administration.

These results indicate that the time dependence of the forced vital capacity manoeuvre has an important impact on the assessment of routine lung function in a clinical setting and supports the notion that the time course of the inspiration preceding the forced vital capacity manoeuvre should be standardised.
High-altitude pulmonary hypertension: a pathophysiological entity to different diseases
Authors: Maggiorini M. , Léon-Velarde F.
Published: September 2008

Pulmonary hypertension is a hallmark of high-altitude pulmonary oedema (HAPE) and of congestive right heart failure in subacute mountain sickness (SMS) and chronic mountain sickness (CMS) in the Himalayas and in the end-stage of CMS (Monge's disease) in the Andes.

There are studies to suggest that transmission of excessively elevated pulmonary artery pressure and/or flow to the pulmonary capillaries leading to alveolar haemorrhage is the pathophysiological mechanism of HAPE.

In the Himalayas, HAPE was successfully prevented by extending the acclimatisation period from a few days to 5 weeks, however, this did not prevent the occurrence of congestive right heart failure after several weeks of stay at 6,000 m. This leads to the concept that rapid remodelling of the small precapillary arteries prevents HAPE but not the development of right heart failure in SMS and CMS.

Unresponsiveness of pulmonary hypertension to oxygen at high altitude and its complete resolution only after weeks of stay at low altitude suggest that structural rather than functional changes are its pathophysiological mechanism. Since pulmonary hypertension at high altitude is the driving force leading to high-altitude pulmonary oedema and “high-altitude right heart failure” in newcomers and residents of high altitude, the authors propose to adjust current terminology accordingly.
Sex differences in lung vulnerability to tobacco smoking
Authors: Langhammer A. , Johnsen R. , Gulsvik A. , Holmen T.L. , Bjermer L.
Published: September 2008

Studies have indicated that females are more vulnerable to the deleterious effect of tobacco smoking than males. The current study aimed to investigate the associations between tobacco smoking and reported respiratory symptoms, self-rated health, and lung function by sex.

In 1995–1997 65,225 subjects aged ≥20 yrs (71% of invited) attended for screening within the Nord-Trøndelag Health Study. Among these, 10,941 subjects selected randomly or because they reported having asthma or asthma-related symptoms, participated in the Bronchial Obstruction in Nord-Trøndelag study consisting of spirometry and a personal interview.

Tobacco smoking was associated with increased prevalence of respiratory symptoms, reduced lung function, and lower score on global self-rated health (SRH). Adjusted for smoking burden and lung function, females had a higher risk for reporting respiratory symptoms and lower SRH compared with males. Further, smoking burden was associated with a larger relative reduction in expiratory lung function in females than in males.

Females reported more symptoms and lower self-rated health compared with males with similar smoking burden. Even if smoking in females was associated with a larger reduction in per cent predicted lung function compared with males, this does not fully explain the higher symptom prevalence in females.
Nutrition and respiratory health in adults: findings from the Health Survey for Scotland
Authors: Kelly Y. , Sacker A. , Marmot M.
Published: September 2008

There is a growing body of evidence to support the hypothesised links between consumption of antioxidant rich foods and the occurrence of obstructive airway disease. The main research question was to examine the relationships between two types of dietary exposure and two indicators of respiratory morbidity in Scottish adults.

The relationships between dietary consumption of fruit, vegetables and fish, and plasma levels of vitamins A, C, E and β-carotene, and pulmonary function (forced expiratory volume in one second (FEV1)) and symptoms (phlegm production and shortness of breath with wheezing), were examined in a random population sample of adults.

A dose/response relationship was found between fruit consumption and pulmonary function. In comparison with eating fruit rarely or never, eating fruit at least once per day, 1–6 times per week, and 1–3 times per month were associated with differences of 132, 100 and 63 mL in FEV1, after adjustment for known confounders and dietary intake of vegetables and fish (n=6186). An sd score change in plasma vitamin C was associated with a 49 mL difference in FEV1(n=930). Fruit and vitamin E were associated with a reduced prevalence of phlegm production for 3 months or more per year.

The most beneficial combination of dietary components may be found in natural foodstuffs, particularly fresh fruit.
The economic impact of preschool asthma and wheeze
Authors: Stevens C.A. , Turner D. , Kuehni C.E. , Couriel J.M. , Silverman M.
Published: September 2008

The aim of the present study was to determine the economic impact in the UK of wheezing disorders in preschool children.

Health, societal and family-borne costs were calculated for a sample of 94 preschool children who attended hospital with a primary diagnosis of wheeze or asthma during 1998/1999. Sample costs were calculated using data from a structured interview schedule and from symptom diaries completed by trial parents, patients' general practice and hospital records, and hospital finance data. Health costs for 1–5-yr-olds inthe UK were calculated using data from a postal population survey in the same region.

It is estimated that 1–5-yr-old children with wheeze in the UK cost the health service a total of 53 million UK pounds (GBP). The greatest expenditure, 34 million GBP, was for primary care, representing 65.2% of total healthcare costs. Prescription costs represented 20.4% (11 million GBP) of total healthcare costs.

Caring for preschool children with wheeze in the UK cost the health service 0.15% of its total budget in 1998/1999. The total costs to society of caring for the 0.88% of preschool children who attended hospital for asthma or wheeze in a year represented a further 2.6 million UK pounds. Primary prevention strategies at the population level promise more cost savings than any attempt at decreasing hospitalisations in those more severely ill.
A prediction rule to identify allocation of inpatient care in community-acquired pneumonia
Authors: España P.P. , Capelastegui A. , Quintana J.M. , Soto A. , Gorordo I. , García-Urbaneja M. , Bilbao A.
Published: September 2008

The current authors developed a new prediction rule based on the five risk classes defined by the Pneumonia Severity Index to identify allocation of inpatient care in community-acquired pneumonia.

The decision to hospitalise in low-risk classes (I−III) was unquestionable, if the presence of one or more of the following were evident: arterial oxygen tension <8.0 kPa (60 mmHg), shock, decompensated coexisting illnesses, pleural effusion, inability to maintain oral intake, social problem, and lack of response to previous adequate empirical antibiotic therapy.

The results at 18 months after implementation of this new prediction rule are reported in a series of 616 patients. The mortality rate was 0.5% in 221 patients treated as outpatientsversus8.9% in 395 patients treated as inpatients. Specific additional criteria for hospitalisation included in the prediction rule were present in 106 of the 178 low-risk patients treated as inpatients, whereas in the remaining 72, the decision to hospitalise was apparently unjustified by the prediction rule. These 72 patients showed a better outcome (significantly shorter hospitalisation, days on intravenous antibiotics, mortality, and complicated course) than high-risk patients and low-risk patients who met the additional specific criteria for deciding hospital admission.

Therefore, admission in these low-risk patients might have been avoided by strict adherence to the new prediction rule. Another relevant finding was that the Pneumonia Severity Index alone did not identify all patients who needed to be admitted to the hospital.
Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis
Authors: Krane M. , Griese M.
Published: September 2008

Surfactant protein D (SP‐D) interacts withAspergillus fumigatusand is strongly increased in the lavage from animals with acute allergic reactions to the fungus, suggesting a central role for SP‐D. As the course of cystic fibrosis (CF) is often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the authors hypothesised that SP‐D may also be increased in serum during an ABPA, potentially assisting in its diagnosis and follow-up.

In 22 patients with CF (11 with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary disease, SP‐D concentrations in serum were assessed by an enzyme immunoassay.

Serum SP‐D in CF patients (130±16 ng·mL−1(mean±sem)) was significantly higher than in the controls without lung disease (66±8 ng·mL−1). During the whole ABPA‐episode, SP‐D level did not change significantly, despite large changes of total serum immunoglobulin E. There was a clear negative correlation between SP‐D concentration and overall lung function,i.e.forced expiratory volume in one second and forced vital capacity.

Serum level of surfactant protein D may be of value to follow pulmonary function and lung injury in cystic fibrosis patients. Surfactant protein D serum levels are not helpful for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis episode, contrary to what was expected from animal experiments.
Long-term follow-up of toluene diisocyanate-induced asthma
Authors: Padoan M. , Pozzato V. , Simoni M. , Zedda L. , Milan G. , Bononi I. , Piola C. , Maestrelli P. , Boschetto P. , Mapp C.E.
Published: September 2008

Eighty-seven cases of occupational asthma induced by toluene diisocyanate (TDI) were diagnosed by an inhalation challenge with TDI and methacholine. After an average follow-up interval of 11 yrs, all subjects were re-examined.

Of the 87 subjects examined, 13 (15%) had remained in the same job, 44 (50.5%) had been removed from exposure for <10 yrs and 30 (34.5%) had been removed for >10 yrs. The proportion of subjects who experienced symptoms of asthma and those who were hyperresponsive to methacholine was significantly lower. Of the patients, 59% used short-acting bronchodilators, 8% long-acting bronchodilators and 18% were on regular inhaled glucocorticoids. Thus, multiple regression analysis showed a positive correlation between forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) at follow-up and FVC and FEV1at diagnosis, and a negative correlation with smoking and with therapy with bronchodilators. Stepwise logistic regression showed that the follow-up provocative dose causing a 20% fall in the FEV1(PD20) could be predicted from baseline PD20.

These results indicate that respiratory symptoms and airway hyperresponsiveness to methacholine persist in subjects removed from exposure to TDI for >10 yrs. A more favourable prognosis was associated with a better lung function and a lower degree of airway hyperresponsiveness to methacholine at diagnosis.
Lung cancer: the importance of seeing a respiratory physician
Authors: Fergusson R.J. , Thomson C.S. , Brewster D.H. , Brown P.H. , Milroy R.
Published: September 2008

Patients with lung cancer present to and are managed by a variety of clinicians. In this study the effect of involvement by a respiratory physician on the diagnosis, staging, treatment and survival of a large unselected group of lung cancer patients was investigated

The study population was derived from the Scottish Cancer Registry. A total of 3,855 patients diagnosed during 1995 with lung cancer were studied. The data were validated and supplemented by references to medical records.

The study found that a respiratory physician had been involved in the initial management of 2,901 (75.3%) patients. These patients were found more likely to have had the cancer diagnosis confirmed by histological methods and to have received active treatment with surgery, radiotherapy or chemotherapy. Survival, 1 yr after diagnosis was higher in patients who saw a respiratory physician (24.4versus11.1%) and benefit was found to have remained 3 yrs after diagnosis (8.1versus3.7%). Although the patients who had not seen a respiratory physician were generally older, and had more extensive disease, after correcting for age, stage and other prognostic factors, the relative hazard ratio of death for those not managed by a respiratory physician was 1.44.

The data from this study supports the recommendations of recent lung cancer guidelines for the early involvement by a respiratory physician.
Changes in bronchoalveolar lavage fluid proteins in sarcoidosis: a proteomics approach
Authors: Sabounchi-Schütt F. , Åström J. , Hellman U. , Eklund A. , Grunewald J.
Published: September 2008

In sarcoidosis, an inflammatory lung disease, the protein profile of bronchoalveolar lavage fluid (BALF) is altered. To study the BALF protein pattern changes in sarcoidosis, samples from six patients and four healthy individuals were analysed by two-dimensional polyacrylamide gel electrophoresis.

A comparison of the protein-spot patterns showed a significantly higher number of protein spots in the pH range 5.5–6.7 in patients compared to controls (472versus384). Furthermore, the number of protein spots in the patients were significantly decreased in the acidic pH range 4.5–5.5 (399versus518). Measurement of the optical density in the gels showed varying expression levels for several protein spots. Seventeen of the altered protein spots were identified, of which seven have previously not been reported for BALF. Many of these are nonplasma proteins involved in the inflammatory and oxidant-antioxidant processes.

In conclusion, the bronchoalveolar lavage fluid protein content is altered in sarcoidosis patients, especially for proteins that are not derived from plasma. The described proteomics approach will in the future be used to asses overall changes in the protein content associated with sarcoidosis and may offer the possibility of identifying disease-specific proteins.
Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease
Authors: Paredi P. , Caramori G. , Cramer D. , Ward S. , Ciaccia A. , Papi A. , Kharitonov S.A. , Barnes P.J.
Published: September 2008

In chronic obstructive pulmonary disease (COPD) there is decreased vascularity of the bronchi and inflammation of the airways that may have opposite effects on the regulation of heat loss.

Exhaled air temperature increase (Δe°T) was measured in 23 patients with moderate COPD (18 male, mean age±sem 70±1 yrs; forced expiratory volume in one second (FEV1) 45±3%, FEV1/forced vital capacity 54±4%) and 16 normal volunteers (64±4 yr) and compared to exhaled nitric oxide (eNO) and inflammatory cells in induced sputum as a marker of airway inflammation. Δe°T was measured during a flow- and pressure-controlled single exhalation with a fast-response thermometer.

Δe°T was reduced in patients with COPD (1.86±0.15 Δ°C·s−1) compared to normal subjects (4.00±0.26 Δ°C·s−1). There was no difference in Δe°T between patients treated with inhaled steroids and those who were steroid naïve. Δe°T was correlated with eNO (r=0.60) but not with sputum neutrophilia. In COPD patients, Δe°T was increased (2.26±0.16 Δ°C·s−1) after the inhalation of 200 µg of albuterol, which is a known vasodilator, indicating that Δe°T and bronchial blood flow may be correlated.

Exhaled temperature increase is reduced in chronic obstructive pulmonary disease patients and is increased by the inhalation of vasodilators and therefore may be related to changes of bronchial blood flow and tissue remodelling.
Sleep hypoventilation in hypercapnic chronic obstructive pulmonary disease: prevalence and associated factors
Authors: O'Donoghue F.J. , Catcheside P.G. , Ellis E.E. , Grunstein R.R. , Pierce R.J. , Rowland L.S. , Collins E.R. , Rochford S.E. , McEvoy R.D.
Published: September 2008

Sleep hypoventilation (SH) may be important in the development of hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD). The prevalence of SH, associated factors, and overnight changes in waking arterial blood gases (ABG), were assessed in 54 stable hypercapnic COPD patients without concomitant sleep apnoea or morbid obesity.

Lung function assessment, anthropomorphic measurements, and polysomnography with ABG measurement before and after sleep were conducted in all patients. Transcutaneous carbon dioxide tension (Pt,CO2) was measured in sleep, using simultaneous arterial carbon dioxide tension (Pa,CO2) forin vivocalibration and to correct for drift in the sensor.

Of the patients, 43% spent ≥20% of sleep time withPt,CO2>1.33 kPa (10 mmHg) above waking baseline. Severity of SH was best predicted by a combination of baselinePa,CO2, body mass index and per cent rapid-eye movement (REM) sleep. REM-related hypoventilation correlated significantly with severity of inspiratory flow limitation in REM, and with apnoea/hypopnoea index.Pa,CO2increased mean±sd 0.70±0.65 kPa (5.29±4.92 mmHg) from night to morning, and this change was highly significant. The change inPa,CO2was strongly correlated with severity of SH.

Sleep hypoventilation is common in hypercapnic chronic obstructive pulmonary disease, and related to baseline arterial carbon dioxide tension, body mass index and indices of upper airway obstruction. Sleep hypoventilation is associated with significant increases in arterial carbon dioxide tension night-to-morning, and may contribute to long-term elevations in arterial carbon dioxide tension.
Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children
Authors: Kharitonov S.A. , Gonio F. , Kelly C. , Meah S. , Barnes P.J.
Published: September 2008

Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FENO), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FENOmeasurements is unknown.

The reproducibility, day­to­day, diurnal variation and perception of standardised FENOmeasurements were examined in 59 subjects (40 children aged 7–13 yrs and 19 adults aged 18–60 yrs), both healthy (n=30) and with mild (n=29) asthma. FENOwas measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children.

The coefficient of reproducibility expressed as the mean pooled standard deviation (n=59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FENOwas significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day­to­day variation, or a learning effect, as the result of FENOmeasurements were identical at results of the beginning and at the end of the study.

It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day­to­day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.
Replacement of physiologically autoinhaled nitric oxide in intubated patients
Authors: Röhrig L. , Kuhlen R. , Baumert J. , Rossaint R.
Published: September 2008

Autoinhaled nitric oxide (NO) is produced mainly in the upper airways. Orotracheal intubation disrupts the natural autoinhalation of NO from the naso- and oropharynx. The effect of disrupting and then replacing autoinhaled NO on arterial oxygenation was investigated in intubated patients.

Two groups of nine patients without lung disease were examined during anaesthesia using an inspired oxygen fraction of 0.50. In both groups, the individually produced NO of the whole respiratory tract and the upper airways was determined. The amount of NO normally autoinhaled from the upper airways was replaced for 5 min after orotracheal intubation in one group.

The amount of NO from the upper respiratory tract was 47±19 parts per billion (ppb) in the test group and the replaced NO concentration was 48±20 ppb. No significant increase in arterial oxygen tension could be detected during the replacement of the autoinhaled NO. Haemodynamic parameters remained unchanged. In the control group, the NO from the upper airways was 34±16 ppb. In contrast to the test group, it was not replaced after intubation.

These findings suggest that in healthy subjects the autoinhalation of nitric oxide does not play an important role in arterial oxygenation during anaesthesia.
Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma
Authors: Babu K.S. , Woodcock D.A. , Smith S.E. , Staniforth J.N. , Holgate S.T. , Conway J.H.
Published: September 2008

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant.

Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period.

Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0–2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1for EAR was 4.19% and 23.98% in the PT and the NT group, respectively.

The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.
Relationship between FEV1reduction and respiratory symptoms in the general population
Authors: Jakeways N. , McKeever T. , Lewis S.A. , Weiss S.T. , Britton J.
Published: September 2008

Obstructive airways diseases typically present with dyspnoea, cough and wheeze, and are defined by a reduced forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio. Traditionally, however, the severity of chronic obstructive pulmonary disease is graded by the FEV1% predicted rather than the FEV1/FVC ratio, whilst other potentially valid measures of FEV1impairment, such as the absolute difference of FEV1from predicted or the absolute level of FEV1, tend not to be used. The authors have therefore explored the relationship between these different measures of FEV1impairment and chronic respiratory symptoms in a general population sample.

FEV1and FVC were measured and questionnaire data were obtained on cough, wheeze, shortness of breath and general self-reported breathing trouble in a cross-sectional survey of 2,633 adults aged 18–70 yrs from a district of Nottingham, UK. Odds ratios for each symptom were calculated for declining levels of absolute FEV1, FEV1% pred, absolute difference of FEV1from predicted, and FEV1/FVC ratio. They were plotted to display the shape and strength of these relationships before and after adjustment for each other measure.

The odds of symptoms increased with declining levels of all FEV1measures, particularly for wheeze and general breathing trouble. Although this study was not sufficiently powerful to detect significant differences between measures, these relationships were consistently strongest, before and after adjustment, for FEV1% pred, particularly below a threshold of ∼75%.

The authors conclude that forced expiratory volume in one second % predicted appears to be the measure of airflow impairment most closely associated with chronic respiratory symptoms in the general population.
Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy
Authors: Bottini P. , Dottorini M.L. , Cristina Cordoni M. , Casucci G. , Tantucci C.
Published: September 2008

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41–50) yrs; body mass index (BMI) 24.1 (22–26) kg·m−2) and eight without autonomic neuropathy (DAN−) (age 45 (35–55) yrs; BMI 24.8 (23–26) kg·m−2)) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed.

DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH−; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36–48) yrs; BMI 24.4 (23–25) kg·m−2).

In contrast to DAN− and controls, who did not show SDB, five DAN+ (four DAN+PH− and one DAN+PH+) had an apnoea/hypopnoea index ≥10 and four DAN+ (two DAN+PH− and two DAN+PH+) had an apnoea index ≥5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation <90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2chemosensitivity.

In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency >30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.
Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids
Authors: Mendes E.S. , Pereira A. , Danta I. , Duncan R.C. , Wanner A.
Published: September 2008

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma.

A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean±sdQawnormalised for anatomical dead space was 53.1±1.4 µL·min−1·mL−1in healthy subjects (n=10) and 67.8±3 µL·min−1·mL−1in asthmatics (n=10).

All GS caused a transient decrease inQaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decreaseQawby 20% from the baseline, 30-min postdrug inhalation.

Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.
Methodological issues in evaluating measures of health as outcomes for COPD
Authors: Jones P.W. , Kaplan R.M.
Published: September 2008

The selection of an appropriate outcome measure depends on the aspect of the disease being addressed and the purpose of the study being conducted. The most fundamental property of any outcome is its ability to measure the biological variable under question. Other properties such as discriminative and evaluative abilities are also important.

Specific outcomes measure a single biological variable, such as forced expiratory volume in one second or depression. The specificity of such measures is attractive but requires precise definition of what is being measured and why. Other, summative, outcomes are used to quantify the overall effect of a number of different biological processes.

The simplest summative measures are global questions such as “How would you rate your health overall?” Others are complex with many items. If designed and used correctly, these questionnaires can provide an estimate of the overall impact of disease or response to therapy and an index of whether that response was clinically worthwhile.

Standardisation of measurements is important to permit comparisons between patients and studies, which makes the measurement of an individual's “quality of life” difficult. The term “health-status measurement” may be better when referring to the use of standardised questionnaires. Utility-based measures help address concerns regarding clinicalversusstatistical improvement and place outcomes for chronic obstructive pulmonary disease treatment trials in the context of all healthcare treatments.