bluuebunny/crossref_metadata_2025 huggingface dataset:
Results from 8 yrs of susceptibility testing of clinical Mycobacterium tuberculosis isolates in Denmark
Authors: Thomsen VO , Bauer J , Lillebaek T , Glismann S
Published: July 2002

Increased rates of multidrug-resistant (MDR) tuberculosis (TB) has been reported from countries close to Denmark. This study evaluated the incidence of drug resistance in Denmark in order to determine the magnitude of the problem. Susceptibility testing was performed in isolates from 85.4% of all notified patients during 1991-1998. Epidemiological information was retrieved from the mandatory notification forms. Total drug resistance remained largely constant, although a minor increase was observed in 1997-1998. Monoresistance was observed in 7.3%, of the isolates. Among 3.6% polyresistant isolates, resistance to isoniazid and streptomycin accounted for 2.8%, whereas MDR accounted for 0.5%. The MDR strains displayed different restriction fragment length polymorphism (RFLP) patterns, and no matches were identified in the international MDR database. Drug resistance in untreated Danes and foreigners were 5.9% and 14.6%, respectively. Among Danes and foreigners with previous TB, 6.2% and 22.7% had drug resistance, respectively. Increased drug-resistance was found among untreated Danes aged 25-54 yrs mainly due to a single isoniazid and streptomycin-resistant RFLP-cluster. Among all patients with isoniazid and streptomycin-resistance, 77.0% had clustered strains. In conclusion, although drug resistance among untreated Danes was close to the rate estimated in good national programmes, close monitoring is needed in future years, as active transmission of isoniazid- and streptomycin-resistant Mycobacterium tuberculosis was demonstrated.
Enhancing care for people with asthma: the role of communication, education, training and self-management. 1998 World Asthma Meeting Education and Delivery of Care Working Group
Authors: Partridge MR , Hill SR
Published: July 2002

Reduction in the morbidity associated with asthma requires attention to several aspects of the behaviour of health professionals and patients, and to the interactions between these two groups. In this review, what has been learnt about health professional/patient communication and patient education (skills, settings and materials), lay and health professional liaison (including telephone helplines), patient education in low-income countries, the integration of patient education into clinical practice, health professional training and the implementation of guidelines, and the role of national asthma campaigns is drawn together. What changes in public policy would enhance asthma care, and whether the promotion of asthma self-management skills is cost effective are also considered. It is concluded that, although further research is necessary in many areas, well-educated health professionals who recognize the person with asthma as an individual, and who give advice about self-management, can significantly reduce the suffering and costs associated with asthma.
Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler
Authors: Bousquet J , D'Urzo A , Hebert J , Barraza CH , Boulet LP , Suarez-Chacon R , Harnest U , Lundback B , Martinez Morales G , Nieminen MM , Nolop KB , Visser S , Lutsky BN
Published: July 2002

Mometasone furoate (MF) administered by dry powder inhaler (DPI) was composed with budesonide (BUD) Turbuhaler in the treatment of moderate persistent asthma. The patients were randomized to one of four treatment groups: MF DPI (100, 200, 400 microg b.i.d) or BUD Turbuhaler. 400 microg b.i.d in a 12-week, active-controlled, evaluator-blind, multicentre international trial. The primary efficacy variable was the mean change from baseline to endpoint (last treatment visit) in forced expiratory volume in one second (FEV1). Changes in FEV1 showed a statistically significant superiority (p<0.05) of MF DPI 200 and 400 microg b.i.d compared with the BUD Turbuhaler 400 microg b.i.d treatment. Significant superiority (p<0.05) was also seen in scores for several secondary efficacy variables when MF DPI was compared with BUD Turbuhaler treatment. MF DPI 200 microg b.i.d was comparable to MF DPI 400 microg b.i.d in therapeutic benefit. The incidence of oral candidiasis was no more than 3% in any group. All treatments were well tolerated. A total daily dose of 400 microg of mometasone furoate administered by dry powder inhaler provides a well-tolerated treatment for patients with moderate persistent asthma and results in a significantly greater improvement, when compared to a daily dose of 800 microg BUD Turbuhaler in the parameters measured in this study.
Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo
Authors: Middelveld RJ , Zetterquist WC , Bergman D , Alving K
Published: July 2002

The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen- and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO. Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with N(G)-nitro-L-arginine (L-NA, 10 mg x kg(-1)), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment. It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0-90 min were (mean+/-SEM) 1,119+/-160 versus 555+/-56 (cmH2O x L(-1) x s(-1) x min for controls, p<0.05 (Mann-Whitney U-test), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.85+/-0.43 versus 0.31+/-0.06 g x L(-1), p<0.01) and histamine levels (42.8+/-16.0 versus 2.6+/-0.8 nM, p<0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge. In conclusion, this study showed that N(G)-nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide.
Aerosol delivery from spacers in wheezy infants: a daily life study
Authors: Janssens HM , Heijnen EM , de Jong VM , Hop WC , Holland WP , de Jongste JC , Tiddens HA
Published: July 2002

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.
Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study
Authors: Rasmussen F , Lambrechtsen J , Siersted HC , Hansen HS , Hansen NC
Published: July 2002

Intense physical activity in children may either improve fitness and protect against asthma, or may trigger symptoms. The aim of this study was to determine whether physical fitness in childhood has an impact on the development of asthma. In this prospective, community-based study, 757 (84%) asymptomatic children with an average age at inclusion of 9.7 yrs were followed for 10.5 yrs. In both surveys a maximal progressive exercise test on a bicycle ergometer was used to measure physical fitness (maximal workload) and to induce airway narrowing. A methacholine provocation test was performed in the subjects at follow-up. During the 10-yr study period, 51 (6.7%) of the previously asymptomatic children developed asthma. These subjects had a lower mean physical fitness in 1985 than their peers: (3.63 versus 3.89 W x kg(-1); p=0.02) in boys and (3.17 versus 3.33 W x kg(-1); p=0.02) in girls. A weak correlation was found between physical fitness in childhood and airway responsiveness to methacholine at follow-up when adjusted for body mass index, age and sex (r=0.11; p<0.01). In a multiple regression analysis, physical fitness was inversely related to the development of physician diagnosed asthma, odds ratio=0.93 (0.87-0.99). Thus, the risk for the development of asthma during adolescence is reduced 7% by increasing the maximal workload 1 W x kg(-1). In conclusion, this study showed that physical fitness in childhood is weakly correlated with the development of asthma during adolescence and that high physical fitness seems to be associated with a reduced risk for the development of asthma.
T-cell receptor repertoire expression in workers with occupational asthma due to platinum salt
Authors: Raulf-Heimsoth M , Merget R , Rihs HP , Fohring M , Liebers V , Gellert B , Schultze-Werninghaus G , Baur X
Published: July 2002

There is a high incidence of asthma, rhinitis, conjunctivitis and contact urticaria in workers of precious metal refineries. Symptoms are closely associated with sensitization to halogenated platinum compounds, as assessed by skin-prick test. The aim of the present study was to examine the molecular mechanisms involved by describing the T-cell receptor (TCR) repertoire distribution of peripheral blood mononuclear cells (PBMCs) without and after in vitro stimulation with sodium hexachloroplatinate. PBMCs of 17 sensitized subjects with work-related asthma and a positive skin-prick test result to sodium hexachloroplatinate and of 15 nonexposed subjects were isolated and TCR expression determined by flow cytometry. Furthermore, the sodium hexachloroplatinate-mediated in vitro effects on the frequency of Vbeta-expressing T-cells, the proliferation response and the expression of cell surface molecules like CD71, CD25, CD95 and HLA-DR were studied. CD3-positive lymphocytes of platinum salt-sensitized workers had a significantly higher frequency of Valpha2a+, Vbeta11+ and Vbeta21.3+ T-cells than controls (p<0.01, p<0.01 and p<0.001 respectively). In vitro stimulation of PBMCs from platinum salt-sensitized as well as control subjects with sodium hexachloroplatinate increased the percentage of CD3-positive cells bearing specific TCRs, especially Vbeta5.3, Vbeta6.7, Vbeta8a, Vbeta20 and Vbeta21.3. This effect was time- and dose-dependent. The present results indicate that the frequencies of Valpha2a-, V11 and Vbeta21.3-bearing blood T-cells and platinum salt-induced lymphocyte proliferation are strongly enhanced in subjects who suffer from asthma due to platinum salt. In addition, in vitro stimulation with sodium hexachloroplatinate modulates the frequencies of certain T-cell receptor-bearing T-cells.
Effects of ambient ozone on lung function in children over a two-summer period
Authors: Kopp MV , Bohnet W , Frischer T , Ulmer C , Studnicka M , Ihorst G , Gardner C , Forster J , Urbanek R , Kuehr J
Published: July 2002

There is a general consensus that short term exposure to ozone (O3) causes a decrease in lung function parameters such as forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). The objective of this study was to assess the reproducibility of lung function decrements after ambient O3 exposure over a two-summer period. The authors studied 797 children with a mean age of 8.2 yrs (95% confidence interval: 6.9-9.5) from the second and third grades of ten elementary schools in Austria and southwestern Germany. At the outset the various study locations were stratified into three groups with low (L), medium (M) and high (H) O3 exposure (range of mean O3 concentration in the locations April-October 1994: 24-30 (L); 33-38 (M); 44-52 (H) parts per billion (ppb)). Four lung function tests were performed on each child between March 1994 and November 1995. The increases in FVC and FEV1 recorded from one test period to the next were expressed as mL x day(-1). A significantly lower FVC and FEV1 increase was observed in children exposed to high ambient O3 concentration during the summer season. (FVC in summer 1994: 0.83 (L); 0.56 (M); 0.55 (H) mL x day(-1); p=0.004; and summer 1995: 0.80 (L); 0.63 (M); 0.56 (H) mL x day(-1); p=0.011; FEV1 in summer 1994: 0.48 (L); 0.34 (M); 0.18 (H) mL x day(-1); p=0.004 and summer 1995: 0.68 (L); 0.45 (M); 0.41 (H) mL x day(-1), p=0.006). There was no significant difference in FVC or FEV1 increase between the groups during the winter period. Adjusting for sex, age, height and passive smoke exposure, linear regression revealed a statistically significant negative association of average ambient O3 concentration with the FVC and FEV1 increase in both summers. During the winter period no association of O3 with FVC or FEV1 was observed. In conclusion, in two consecutive summer periods the authors found reproducible lung function decrements in children exposed to high levels of ambient ozone. Reoccurrence of ozone associated lung function deficits might increase the likelihood of persisting effects on the childrens' airways.
Expression of GATA family of transcription factors in T-cells, monocytes and bronchial biopsies
Authors: Caramori G. , Lim S. , Ito K. , Tomita K. , Oates T. , Jazrawi E. , Chung K.F. , Barnes P.J. , Adcock I.M.
Published: July 2002

GATA-binding proteins are a subfamily of zinc finger transcription factors with six members (GATA-1-6) that interact with the GATA deoxyribonucleic acid (DNA) sequence. This sequence is found in the regulatory regions of many genes including those encoding T-helper 2 (Th2)-like cytokines, receptors, adhesion molecules and enzymes, which may be important in the pathogenesis of bronchial asthma.

The expression of GATA-3, -4 and -6 was investigated in peripheral blood T-lymphocytes and monocytes and bronchial biopsies from 11 normal subjects and 10 steroid-naïve asthmatic patients.

Using Western blot analysis, T-cells from asthmatic subjects expressed 5 times the level of GATA-3 compared to that in normals. Confocal microscopy indicated that GATA-3 expression was both nuclear and cytoplasmic. GATA DNA binding complex containing GATA-3 was elevated in Th2 cells as determined by electrophorectic mobility shift assay. In contrast, monocytes from normal and asthmatic subjects expressed GATA-4 and -6 in equal amounts, but no GATA-3 was found. Using immunohistochemistry in bronchial biopsies, epithelial cells expressed high levels of GATA-3, GATA-4 and GATA-6 proteins. Comparison of Western blots of bronchial biopsies showed no significant differences between normal and asthmatic subjects.

In conclusion, the increased expression of GATA-3 in asthmatic T-cells may underlie augmented T-helper 2-like cytokines in this disease. However, the unaltered GATA-3 expression in epithelial cells suggests a distinct role for GATA-3 in these cells unrelated to T-helper 2-like cytokine release. Finally, no evidence was found for an increased expression of GATA-4 and GATA-6 in asthma.
Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis
Authors: Steels E. , Paesmans M. , Berghmans T. , Branle F. , Lemaitre F. , Mascaux C. , Meert A.P. , Vallot F. , Lafitte J.J. , Sculier J.P.
Published: July 2002

The role of p53, as a prognostic factor for survival in lung cancer, is controversial and the purpose of the present systematic review of the literature is to determine this effect.

Published studies were identified with the objective to aggregate the available survival results after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to deal with p53 assessment in lung cancer (primary site) only, and to provide a survival comparison according to the p53 status.

Among the 74 eligible papers, 30 identified p53 abnormalities as a univariate statistically significant poor prognostic factor and 56 provided sufficient data to allow survival results aggregation. There was no significant difference between the trials that either showed or did not show a prognostic effect of p53 according to the methodological score or to the laboratory technique used. The studies were categorized by histology, disease stage, treatment and laboratory technique. Combined hazard ratios suggested that an abnormal p53 status had an unfavourable impact on survival: in any stage nonsmall cell lung cancer (NSCLC) the mean (95% confidence interval) was 1.44 (1.20–1.72) (number of studies included in the subgroup was 11), 1.50 (1.32–1.70) in stages I–II NSCLC (n=19), 1.68 (1.23–2.29) in stages I–IIIB NSCLC (n=5), 1.68 (1.30–2.18) in stages III–IV NSCLC (n=9), 1.48 (1.29–1.70) in surgically resected NSCLC (n=20), 1.37 (1.02–1.85) in squamous cell carcinoma (n=9), 2.24 (1.70–2.95) in adenocarcinoma (n=9), 1.57 (1.28–1.91) for a positive immunohistochemistry with antibody 1801 (n=8), 1.25 (1.09–1.43) for a positive immunohistochemistry with antibody DO-;7 (n=16), and 1.65 (1.35–2.00) for an abnormal molecular biology test (n=13). Data were insufficient to determine the prognostic value of p53 in small cell lung cancer.

In each subgroup of nonsmall cell lung cancer, p53 abnormal status was shown to be associated with a poorer survival prognosis.
Efficacy of daytime continuous positive airway pressure titration in severe obstructive sleep apnoea
Authors: Rudkowski J.C. , Verschelden P. , Kimoff R.J.
Published: July 2002

The aim of this study was to evaluate manual nasal continuous positive airway pressure (nCPAP) titration during daytime polysomnography compared with conventional overnight titration for patients with severe obstructive sleep apnoea.

Thirty-two patients who underwent daytime titration were retrospectively matched (for age, sex, body mass index and apnoea/hypopnoea index (AHI)) to a group titrated overnight during the same period. Successful titration was defined as the identification of the nCPAP level (effective nCPAP (Peff)) required to eliminate respiratory events during all sleep stages. After 3 months of therapy on nCPAP atPeff, nCPAP utilization history was obtained and a group of patients underwent a repeat polysomnogram (PSG) and completed a follow-up Epworth Sleepiness Scale (ESS) score.

Initial titration was successful in 91% of daytime patients and 91% of overnight patients. The success of daytime titration was not related to diagnostic AHI or ESS score. Subjective nCPAP utilization was statistically similar in both groups. On the follow-up PSG, there were no significant differences between daytime (n=11) and overnight (n=11) patients in measures of sleep quality or respiratory disturbance. Both groups demonstrated similar and significant improvements in ESS score.

These findings suggest that the effective nasal continuous positive airway pressure can be accurately established during daytime titration in a substantial proportion of severe, symptomatic obstructive sleep apnoea patients.
Memory for symptoms in COPD patients: how accurate are their reports?
Authors: Meek P.M. , Lareau S.C. , Anderson D.
Published: July 2002

The purpose of this study was to examine the accuracy of self-reports of symptom intensity in patients with chronic obstructive pulmonary disease (COPD) and factors that might influence recall of that intensity.

Thirty COPD (forced expiratory volume in one second (FEV1) 36±17% predicted) subjects recorded their dyspnoea and fatigue intensity scores on a 0–10 scale for 14 consecutive days. On the fourteenth day, subjects recalled their average, greatest and least symptom intensity for the previous 14 days. General cognitive function, spirometry, and oxygenation were also measured.

No significant differences were found between actual and recalled scores for dyspnoea or fatigue. General cognitive function, measured by the Mini Mental State Exam, correlated with the greatest and least dyspnoea and average fatigue difference scores (recall-actual) and contributed to the variance in the average and least dyspnoea recalled scores. The greatest contributor to the variance in the recall scores of both symptoms was the symptom intensity level on the day of recall.

These results highlight the importance of current levels of symptom intensity and cognitive function when appraising symptoms in chronic obstructive pulmonary disease patients.
The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics
Authors: Solèr M. , Matz J. , Townley R. , Buhl R. , O'Brien J. , Fox H. , Thirlwell J. , Gupta N. , Della Cioppa G.
Published: July 2002

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma.

After a run-in period, 546 allergic asthmatics (aged 12–76 yrs), symptomatic despite inhaled corticosteroids (500–1,200 µg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable.

Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab groupversusthe placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups.

These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.
Respiratory symptoms in relation to indoor exposure to mite and cat allergens and endotoxins
Authors: Gehring U. , Heinrich J. , Jacob B. , Richter K. , Fahlbusch B. , Schlenvoigt G. , Bischof W. , Wichmann H-E.
Published: July 2002

The authors investigated the relationship between respiratory symptoms in adults and exposure to mite and cat allergens, the role of endotoxins in house dust, the effects of mixtures of several allergens, and interactions between allergen exposure and allergic sensitization.

Within a nested case-control study, 405 subjects aged 25–50 yrs from two German cities answered a standardized questionnaire. Allergen-specific immunoglobulin-E was measured. Dust samples were taken from the subjects' homes to determine exposure to mite (Dermatophagoides pteronyssinusantigen 1Der p1) and (D. farinaeantigen 1Der f1) and cat (cat antigen d1Fel d1) allergen and endotoxin content in settled house dust.

Exposure toDer f1 andDer p1 plusDer f1 >10 µg·g−1of mattress dust, respectively, increased the risk of wheeze and breathlessness (odds ratios (OR): 4.04, 95% confidence interval (CI): 1.53–10.64, OR: 2.78, 95% CI: 1.06–7.28).Fel d1 >8 µg·g−1was positively associated with cough at night (OR: 2.74, 95% CI: 1.22–6.17), noteworthy also in the nonsensitized subjects. Subjects exposed to elevated concentrations of more than one allergen had an up to seven-fold increase in the risk of respiratory symptoms, compared to nonexposed subjects. Sensitized subjects exposed to elevated concentrations ofDer f1 orFel d1 were found to have the highest risk of asthma attacks and respiratory symptoms. No statistically significant association was found between exposure to endotoxins and respiratory health.

Indoor exposure toDermatophagoides farinaeantigen 1 and cat antigen d1 is a risk factor for respiratory symptoms in adults, and for cat antigen d 1 even in nonsensitized subjects. The risk is increased if subjects are exposed to a mixture of allergens or if they are sensitized in addition to high exposure.
Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders
Authors: Roponen M. , Kiviranta J. , Seuri M. , Tukiainen H. , Myllykangas-Luosujärvi R. , Hirvonen M-R.
Published: July 2002

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building.

Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-α in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure.

The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 pg·mL−1, range 0–206.5 pg·mL−1), as compared to that during vacation (0.4 pg·mL−1, range 0–3.7 pg·mL−1) (p=0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p=0.028).

In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.
Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep
Authors: Saaresranta T. , Polo-Kantola P. , Rauhala E. , Polo O.
Published: July 2002

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing.

Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later.

At baseline, the overnight mean±sd end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5±0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0±1.2%,Sa,O2nadir 80.0±6.7%, and frequency of oxygen desaturation ⩾4% (ODI4) per hour 2.2±1.3. MPA decreasedPet,CO2by 0.8 kPa (14.5%, p<0.001). After washout, the meanPet,CO2remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline.Sa,O2did not change.Pet,CO2was lower on MPA than on nCPAP (4.7±0.2 kPaversus5.0±0.3 kPa; p=0.037) butSa,O2was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA.

Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks post-treatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.
Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes
Authors: Purokivi M.K. , Hirvonen M-R. , Randell J.T. , Roponen M.H. , Meklin T.M. , Nevalainen A.I. , Husman T.M. , Tukiainen H.O.
Published: July 2002

Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood.

In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-α (TNF-α) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday.

The authors found a significant elevation of IL-1, TNF-α and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings.

The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.
Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis
Authors: Roberts C. , Devenny A.M. , Brooker R. , Cockburn J.S. , Kerr K.M.
Published: July 2002

An unusual case of endobronchial polyposis associated with extensive bronchiectasis in the context of cystic fibrosis (CF) has been described.

A 15-yr-old female patient with CF underwent partial pneumonectomy for extensive bronchiectasis and frequent infective pulmonary exacerbations.

Cylindrical bronchiectasis with associated purulent bronchitis and bronchiolitis, together with inflammatory polyposis, was noted in the resected lung.

To the best of the authors' knowledge, this is the first report of multiple endobronchial polyposis and may represent a rare complication of bronchiectasis in a patient with cystic fibrosis. On-going infection and the cellular composition of the polyps are discussed in relation to their possible aetiological relevance and relationship to upper respiratory tract polyps.
Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies
Authors: Lewis S.A. , Weiss S.T. , Britton J.R.
Published: July 2002

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community.

Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression.

Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20provided the best sensitivity for specificity (61% for 95% at 8.3 µmol). In those aged ⩾50 yrs, no measure was closely related to diagnosed asthma.

In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.
Virtual tools for imaging of the thorax
Authors: Ferretti G.R. , Bricault I. , Coulomb M.
Published: July 2002

Helical computed tomography (HCT) allows for volume acquisition of the entire thorax during a single apnoea. Combination of HCT acquisition with synchronous vascular enhancement gives rise to HCT angiography (HCTA).

In the last decade, HCT and HCTA have revolutionized the diagnosis of thoracic diseases, modifying many diagnostic algorithms. Because HCT provides for a true volume acquisition free of respiratory misregistration, three-dimensional (3D) rendering techniques can be applied to HCT acquisitions.

As these 3D rendering techniques present the HCT information in a different format to the conventional transaxial CT slices, they can be summarized as virtual tools.

The purpose of this review is to give the readers the most important technical aspects of virtual tools, to report their application to the thorax, to answer clinical and scientific questions, and to stress their importance for patient management, clinical decision making, and research.
Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics
Authors: Fukunaga K. , Asano K. , Mao X‐Q. , Gao P‐S. , Roberts M.H. , Oguma T. , Shiomi T. , Kanazawa M. , Adra C.N. , Shirakawa T. , Hopkin J.M. , Yamaguchi K.
Published: July 2002

Whole genome scan analyses have revealed that chromosomal region 3p21−24, which contains a gene cluster of CC chemokine receptors such as CCR3, is possibly linked to asthma. Because CCR3 ligands play a pivotal role in the selective recruitment and activation of inflammatory cells in the asthmatic airway, the authors examined whether there is any association between asthma and the CCR3 gene polymorphisms.

Three polymorphisms were identified using the single stranded conformational polymorphism method in Japanese (Asian) and British (Caucasian) subjects; one silent mutation T51C and two missense mutations G824A and T971C. These polymorphisms were examined in 391 Japanese subjects (210 asthmatics and 181 nonasthmatic controls) and 234 British subjects (142 asthmatics and 92 nonasthmatic controls). Asthma diagnosis was based on episodic symptoms, documented wheeze, and the presence of reversible airflow limitation.

CCR3 T51C demonstrated a significant association with the diagnosis of asthma in the British population (odds ratio 2.35, p<0.01), but not in the Japanese population. Multiple logistic regression analysis also showed that CCR3 T51C was associated with asthma (odds ratio 2.83, p<0.02), independent of atopic phenotypes such as high levels of total or house dust mite-specific immunoglobulin-E in serum.

In conclusion, a significant association between asthma and CCR3 T51C polymorphism localized on chromosome 3p21 was found.
In vitroassessment of equipment and software to assess tidal breathing parameters in infants
Authors: Schmalisch G. , Foitzik B. , Wauer R.R. , Stocks J.
Published: July 2002

The aim of thisin vitrostudy was to compare the measurement accuracy of two currently available devices for measuring tidal breathing in infants.

A mechanical model pump was used to generate flow profiles which simulated those observed in infants. A range of flows was applied simultaneously to two different devices, namely the commercially available SensorMedics 2600 (SM 2600) and more recently developed, custom-made equipment based on the flow-through technique (FTT). Automatically derived values from both devices were compared with one another and with manual calculations of printouts of the same breaths.

There were no differences in the raw flow signal obtained from the two devices, nor between values calculated automatically or manually from the FTT. Similarly, the deviations between the FTT and SM 2600 were <3% for tidal volume, respiratory frequency and minute ventilation. However, when comparing either with manually calculated values or those derived automatically from the FTT, there was a systematic and highly significant underestimation of shape-dependent parameters, such as the time to peak tidal expiratory flow as a proportion of tidal expiratory time (tPTEF/tE), derived by the SM 2600. The lower the applied flow, the higher the observed deviations, the underestimation being up to 60% when flows simulating those observed in preterm neonates were applied.

These errors appear to result from differences in signal processing such as the algorithms used for breath detection and can only be detected if appropriate nonsinusoidal flow profiles representing those seen in infants are used to evaluate equipment.
Effect of apparatus dead space on breathing parameters in newborns: “flow-through”versusconventional techniques
Authors: Schmalisch G. , Foitzik B. , Wauer R.R. , Stocks J.
Published: July 2002

Commercial devices for tidal breathing measurements in newborns allow only short-term measurements, due to the high apparatus dead space of the face mask and pneumotachometer. The flow-through technique (FTT) minimizes the dead space by a background flow, thereby allowing long-term measurements. The aim of this study was to investigate the comparability of tidal breathing parameters using both techniques.

Paired measurements of tidal breathing were performed in 86 sleeping infants (median (range) body weight 2.8 kg (1.9–5.3 kg), age 65 days (3–150 days)), using the FTT and SensorMedics 2600 (SM 2600).

There was a significant bias (p<0.001) in all tidal breathing parameters. Compared with the FTT, increases (95% confidence interval (CI)) in tidal volume (VT), respiratory frequency (fR), and minute ventilation (V′E) were 0.74 (0.5–1.0) mL·kg−1, 9.0 (6.9–11.2)·min−1and 92 (74–109) mL·min−1·kg−1when measured with the SM 2600, representing average increases of 13, 17 and 30%, respectively, in response to the added dead space. By contrast, time to peak tidal expiratory flow as a proportion of expiratory time (tPTEF/tE) was changed by −0.09 (−0.11–−0.08). The mean (95% CI) change intPTEF/tEof −54 (−62–−45)%, when measured in infants by the SM 2600, was remarkably similar to that observed duringin vitrovalidation studies (−59 (−73–−44)%), suggesting that the discrepancies in timing parameters may be largely attributable to differences in signal processing.

In conclusion, differences in measurement technique and precision of the devices used can result in significant differences in tidal breathing parameters. This may impede the comparison of results within and between infants and the clinical interpretation of tidal breathing measurements in newborns.
Leak compensation in positive pressure ventilators: a lung model study
Authors: Mehta S. , McCool F.D. , Hill N.S.
Published: July 2002

Leak compensating abilities of six different positive pressure ventilators commonly used to deliver noninvasive positive pressure ventilation, including the bilevel positive airway pressure (BiPAP) S/T-D and Quantum (Respironics Inc, Murrysville, PA, USA), 335 and O'NYX (Mallinckrodt Inc, St Louis, MO, USA), PLV 102 (Respironics), and Siemens Servo 900C (Siemens Inc, Danvers, MA, USA).

Using a test lung model, compensatory capabilities of the ventilators were tested for smaller and larger leaks using the assist/control or timed modes. Back-up rate was 20·min−1, inspiratory pressure was 18 cmH2O, and expiratory pressure was 5 cmH2O.

It was found that even in the absence of air leaking, delivered tidal volume differed substantially between the ventilators during use of pressure-targeted modes, depending on inspiratory flows, inaccuracies in setversusdelivered pressures, and inspiratory duration. Also during pressure-targeted ventilation, increasing thetI/ttotup to, but not beyond, 0.5 improved compensation by lengthening inspiratory duration, whereas use of a sensitive flow trigger setting tended to cause autocycling during leaking, interfering with compensation. Leaking interfered with cycling of the BiPAP S/T, inverting the I:E ratio, shortening expiratory time, and reducing delivered tidal volume. Volume-targeted modes achieved limited compensation for small air leaks, but compensated poorly for large leaks.

To conclude, leak-compensating capabilities differ markedly between ventilators but pressure-targeted ventilators are preferred for noninvasive positive pressure ventilation in patients with substantial air leaking. Adequate inspiratory flows and durations should be used, triggering sensitivity should be adjusted to prevent autocycling, and a mechanism should be available to limit inspiratory time and avoid I:E ratio inversion.
Functional differences in bi-level pressure preset ventilators
Authors: Highcock M.P. , Shneerson J.M. , Smith I.E.
Published: July 2002

The performance of four bilevel positive pressure preset ventilators was compared.

The ventilators tested were; BiPAP ST30 (Respironics); Nippy2 (B+D Electrical); Quantum PSV (Healthdyne); and Sullivan VPAP II ST (Resmed). A patient simulator was used to determine the sensitivity of the triggering mechanisms and the responses to a leak within the patient circuit, and to changes in patient effort.

Significant differences (p<0.05) between the devices were seen in the trigger delay time and inspiratory trigger pressure. When a leak was introduced into the patient circuit, the fall in tidal volume (VT) was less than ten per cent for each ventilator. The addition of patient effort produced a number of changes in the ventilation delivered. Patient efforts of 0.25 s induced a variable fall inVT. An increase inVTwas seen with some ventilators with patient efforts of 1 s but the effect was variable. Trigger failures and subsequent falls in minute volume were seen with the BiPAP and the Nippy2 at the highest respiratory frequency.

Differences in the responses of the ventilators are demonstrated that may influence the selection of a ventilator, particularly in the treatment of breathless patients with ventilatory failure.
Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas
Authors: Jones A.M. , Dodd M.E. , Webb A.K.
Published: July 2002

Burkholderia cepaciais a plant phytogen and is known as a hardy and versatile organism.

Over the past two decades it has emerged as a pathogen in the cystic fibrosis (CF) community, with devastating effects. Pulmonary colonisation can lead to an accelerated decline in lung function. In some cases, it causes a rapid and progressive pneumonic illness termed “cepaciasyndrome”, which is untreatable and fatal.

B. cepaciais inherently resistant to multiple antibiotics and highly transmissible and virulent strains have been identified. CF patients colonised with the organism have to be segregated from their peers to try to prevent cross-infection.

However, the pathogenicity ofB. cepaciais not limited to CF. Other groups, such as individuals with chronic granulomatous disease and immunocompromised patients are vulnerable and it has caused disease in healthy individuals. However, the agricultural and petrochemical industries are attempting to exploit properties ofB. cepaciafor use as a biopesticide and biodegradation agent.

This article provides an up to date review of clinically based literature on theBurkholderia cepaciacomplex, highlighting clinical management issues for both cystic fibrosis and non-cystic fibrosis patients. The article also addresses the potential conflict between medicine and agriculture on plans to reintroduce strains ofBurkholderia cepaciaback into the environment.
Vascular smooth muscle cell phenotypes in primary pulmonary hypertension
Authors: Mitani Y. , Ueda M. , Komatsu R. , Maruyama K. , Nagai R. , Matsumura M. , Sakurai M.
Published: July 2002

Primary pulmonary hypertension (PPH) is associated with specific structural alterations, including cellular intimal thickening, intimal fibrosis, and plexiform lesions.

To determine the phenotypes of smooth muscle cells (SMCs) in such lesions, the authors conducted an immunohistochemical analysis of lung tissues from two patients with PPH, using two antimuscle actin antibodies, HHF35 and CGA7, and two anti-SMC myosin heavy chain markers, anti-SM1 and anti-SM2 antibodies and related antibodies. Cells that stained positive (+) with HHF35, CGA7, anti-SM1, and anti-SM2 were considered to be SMCs of a mature state. Conversely, those that stained positive with HHF35 and anti-SM1, but weakly positive (+/−) or negative (−) with CGA7 and anti-SM2, were considered to be SMCs exhibiting an immature state.

Cellular intimal thickening was composed of SMCs of an immature phenotype (HHF35+, CGA7+/−, SM1+, SM2+/−), accompanied by the expression of fibronectin and the presence of macrophages; intimal fibrosis contained mature SMCs (HHF35+, CGA7+, SM1+, SM2+); and plexiform lesion consisted of proliferative endothelial cells (von Willebrand factor-positive cells, proliferating cell nuclear antigen-positive cells) and underlying immature SMCs (HHF35+, CGA7−, SM1+, SM2−) associated with fibronectin expression and macrophage infiltration.

These findings suggest that smooth muscle cells with specific phenotypes may contribute to the development of specific vascular lesions in primary pulmonary hypertension.
Erythromycin attenuates an experimental model of chronic bronchiolitisviaaugmenting monocyte chemoattractant protein‐1
Authors: Takahashi T. , Suga M. , Matsukawa A. , Sato K. , Okamoto T. , Ichiyasu H. , Ohkawara S. , Yoshinaga M. , Ando M.
Published: July 2002

The mechanisms underlying the therapeutic efficacy of erythromycin (EM) in diffuse panbronchiolitis (DPB) was investigated. For this purpose, an experimental rabbit model of DPB induced byPseudomonas aeruginosainoculation was employed. Daily administration of EM (3 mg·kg·day−1) led to an increase in the number of macrophages in bronchoalveolar lavage fluid (BALF) at an early phase, while reducing the size of granulomatous lesions at the late phase without affecting the number of viable bacteria recovered from the infected lung.

Reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemical studies showed that monocyte chemoattractant protein (MCP)‐1 was produced in both BALF and infected lung. EM treatment resulted in a significant increase in the level of MCP‐1 in BALF, while reducing that of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐8. EM also increased MCP‐1 messenger ribonucleic acid (mRNA) and protein expression in the infected lung. MCP‐1 blockade abolished the protective effect of EM, as neutralization of MCP‐1 with anti-MCP‐1 antibodies reduced the EM-induced increase in the number of macrophages in BALF, and augmented size of the granulomatous lesions, as compared to control.

The results of the present study suggest that erythromycin attenuates the pulmonary granuloma formation, at least in part, by increasing the production of monocyte chemoattractant protein‐1.