bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic DNA extraction from small amounts of serum to be used for α1-antitrypsin genotype analysis
Authors: Andolfatto S. , Namour F. , Garnier A-L. , Chabot F. , Gueant J-L. , Aimone-Gastin I.
Published: April 2003

If laboratory diagnosis of α1-antitrypsin (α1-AT) deficiency is usually based on its phenotype identification by isoelectric focusing, α1-antiprotease inhibitor (Pi)S and PiZ genotypes can also be determined by deoxyribonucleic acid (DNA)-based methods. Recently, several methods have been described for preparing genomic DNA from serum. The aim of the current study was to determine the Pi allele from serum extracted DNA by polymerase chain reaction (PCR) and to compare these results with those obtained with whole blood extracted DNA.

Serum α1-AT concentration and phenotypic identification were systematically performed in 43 hospitalised patients. Genomic DNA was simultaneously purified from whole blood and from serum. The mutation detection was found using a PCR-mediated site-directed mutagenesis method.

Concerning phenotypic identification, 29 patients were MM homozygotes, 11 were heterozygotes for S (MS=7) or for Z (MZ=4) and three showed a ZZ phenotype. Genotyping analyses gave identical results with serum and whole blood extracted DNA and all the results were in agreement with the phenotyping results.

The authors found that the deoxyribonucleic acid-based test proved to be a reliable tool for α1-antitrypsin deficiency diagnosis and appears to be an alternative for the labour intensive α1-antitrypsin determination by isoelectric focusing. The authors also concluded that this method yields good quality deoxyribonucleic acid from serum, equal to that extracted from whole blood and is helpful in retrospective studies of multiple genetic markers.
Extracts of lung cancer cells reveal antitumour antibodies in sera of patients with lung cancer
Authors: Bazhin A.V. , Savchenko M.S. , Shifrina O.N. , Chikina S.Y. , Goncharskaia M.A. , Jaques G. , Chuchalin A.G. , Philippov P.P.
Published: April 2003

The objective of the present study was to reveal antitumour antibodies in sera of patients with small cell lung cancer (SCLC).

The antibodies in sera of patients with SCLC and other tumours were detected by immunoblotting with whole extracts of SCLC cells as the antigen source. Sera of patients with various pulmonological disorders, irradiated during the liquidation of consequences of the Chernobyl nuclear power plant incident (a high-risk group in lung cancer), were also analysed.

The present authors' found that SCLC sera contain a set (pattern) of antitumour antibodies which are rarely detected in sera of patients with cancers different from SCLC and very rarely, if ever, present in sera of healthy individuals. The sensitivity and the specificity of the pattern are equal to 80% and 91%, correspondingly. In the high-risk group in lung cancer, the frequencies of the antibodies are somewhat lower than the corresponding values in SCLC sera, but significantly larger than those in healthy sera.

The findings of the present study create a basis for clinical application of the antitumour antibodies described.
Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions
Authors: Jiménez Castro D. , Díaz Nuevo G. , Pérez-Rodríguez E. , Light R.W.
Published: April 2003

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count >50%) of different aetiologies.

Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n=221), idiopathic effusions (n=76), parapneumonic effusions (n=35), postcoronary artery bypass graft surgery effusions (n=6), miscellaneous exudative effusions (n=21) and transudative effusions (n=51).

The ADA level reached the diagnostic cut-off for tuberculosis (40 U·L−1) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1and ADA2were measured, and in all these cases (100%) ADA1/ADApcorrectly classified these lymphocytic effusions as nontuberculous (ratio <0.42).

This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level <40 IU·L−1virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminasepcorrectly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.
Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults
Authors: Marcos M.A. , Jiménez de Anta M.T. , de la Bellacasa J.P. , González J. , Martínez E. , García E. , Mensa J. , de Roux A. , Torres A.
Published: April 2003

Streptococcus pneumoniaeis suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests.

In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of theS. pneumoniaeantigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients.

S. pneumoniaeantigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. TheS. pneumoniaeantigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation withS. pneumoniaewas detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive.

The Binax NOW® immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.
The relationship between water vapour saturation of inhaled air and nasal patency
Authors: Lindemann J. , Leiacker R. , Rettinger G. , Keck T.
Published: April 2003

The nasal cavity volume and the temperature of the nasal mucosa are considered to be the most important predictors of nasal conditioning. The aim of this study was to assess the relationship between the intranasal degree of water vapour saturation of inhaled air and nasal patency.

Intranasal humidity values at different locations within the nasal cavity of 15 healthy subjects were compared to nasal airway resistance detected by active anterior rhinomanometry (AAR). Repeated measurements were carried out during one day to obtain varying nasal cavity volumes due to the nasal cycle. The end-inspiratory humidity data were obtained with a miniaturised capacitive humidity sensor at defined detection sites within the anterior nasal segment without interruption of nasal breathing. Measurements were carried out at four different times during one day.

The degree of water vapour saturation did not correlate with the values of the AAR at any intranasal detection site and time of detection during one day.

The study supports the view that there is no correlation between the degree of water vapour saturation within the anterior nasal segment and the nasal resistance during the nasal cycle over the day. Although nasal patency varies because of the nasal cycle, the changes of nasal cavity volume due to the nasal cycle do not seem to influence the degree of water vapour saturation of the inspiratory air.
Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias
Authors: Kuwano K. , Nakashima N. , Inoshima I. , Hagimoto N. , Fujita M. , Yoshimi M. , Maeyama T. , Hamada N. , Watanabe K. , Hara N.
Published: April 2003

Lung epithelial cells are a primary target for reactive oxygen species (ROS). ROS can cause oxidative deoxyribonucleic acid modification, such as 8-hydroxy-deoxyguanosine (8-OHdG). A human homologue of the MutT protein (hMTH1) prevents this modification. Mitochondria are the most important cellular source of ROS and may be susceptible to oxidative damage. The purpose of this study is to investigate oxidative stress and mitochondrial damage in lung epithelial cells from idiopathic interstitial pneumonias (IIPs).

The authors analysed 8-OHdG, hMTH1, and mitochondrial proteins on lung specimens from 13 patients with IIPs consisted of eight patients with usual interstitial pneumonia and five patients with nonspecific interstitial pneumonia using Western blot analysis and immunohistochemistry.

Immunoreactivity for 8-OHdG and hMTH1 was significantly increased in the lung epithelial cells from patients with IIPs compared with controls. The expression of hMTH1 was localised in the nuclear and cytoplasmic, but not the mitochondrial, fraction of lung homogenates. Immunoreactivity for mitochondrial protein and cytochrome c oxidase complex subunit IV was increased in the lung epithelial cells from patients with IIPs compared with controls.

The current study concludes that oxidative stress may participate in epithelial cell damage in idiopathic interstitial pneumonia, and that increased mitochondrial mass may associate with increased reactive oxygen species production in idiopathic interstitial pneumonia.
Community-acquired pneumonia in the elderly: Spanish multicentre study
Authors: Zalacain R. , Torres A. , Celis R. , Blanquer J. , Aspa J. , Esteban L. , Menéndez R. , Blanquer R. , Borderías L.
Published: April 2003

Community-acquired pneumonia (CAP) in the elderly has increased as a consequence of an overall increase of the elderly population. A controversy about the aetiology and outcome of CAP in this population still exists and more epidemiological studies are needed.

A prospective, 12-month, multicentre study was carried out to assess the clinical characteristics, aetiology, evolution and prognostic factors of elderly patients (≥65 yrs) admitted to hospital for CAP. The study included 503 patients (age 76±7 yrs).

The clinical picture lasted ≤5 days in 318 (63%) and the main clinical features were cough (n=407, 81%) and fever (n=380, 76%). Aetiological diagnosis was achieved in 199 (40%) cases, with a definite diagnosis obtained in 164 (33%). Of the 223 microorganisms isolated the main agents found wereStreptococcus pneumoniaein 98 (49%) andHaemophilus influenzaein 27 (14%). A total of 53 patients died (11%) and the multivariate analysis showed the following factors of bad prognosis: previous bed confinement, alteration in mental status, absence of chills, plasma creatinine ≥1.4 mg·dL−1, oxygen tension in arterial blood/inspiratory oxygen fraction ratio <200 at the time of admission, and shock and renal failure during the evolution.

The results of this study may aid in the management of empiric antibiotic treatment in elderly patients with community-acquired pneumonia and the patients who have a greater probability of bad evolution may be identified based on the risk factors.
The influence of lung volume reduction surgery on exercise in patients with COPD
Authors: Dolmage T.E. , Waddell T.K. , Maltais F. , Guyatt G.H. , Todd T.R.J. , Keshavjee S. , van Rooy S. , Krip B. , LeBlanc P. , Goldstein R.S.
Published: April 2003

Although the influence of lung volume reduction surgery (LVRS) on incremental- and constant-power exercise is important in the evaluation of this procedure for patients with chronic obstructive pulmonary disease (COPD), it is rarely reported even in large randomised controlled trials.

This report describes 39 patients with severe COPD ((mean±se) forced expiratory volume in one second 32±2% pred, functional residual capacity 195±6% pred) who participated in a randomised controlled trial of LVRS and who completed incremental exercise tests at 6 months as well as endurance tests (constant power of 25±1 W) at 3, 9 and 12 months.

Peak oxygen uptake (V′o2,pk) was similar between the treatment (n=19) and control groups (n=20) at baseline. After LVRS, the treatment group had a significantly greaterV′o2,pk(mean difference (95% CI) 1.28 (0.07–2.50) mL·kg·min−1) and power (13 (6–20) W). The treatment group achieved a significantly greater minute ventilation (7.1 (2.9–11.3) L·min−1) with a greater tidal volume (0.16 (0.04–0.28) L). Baseline endurance was similar between groups. After surgery, there were significant between-group differences in endurance time, which were maintained at 12 months (7.3 (3.9–10.8) min).

Lung volume reduction surgery is associated with an increase in exercise capacity and endurance, as compared with conventional medical treatment.
Region-related risk factors for respiratory symptoms in European and Californian farmers
Authors: Monsó E. , Schenker M. , Radon K. , Riu E. , Magarolas R. , McCurdy S. , Danuser B. , Iversen M. , Saiki C. , Nowak D.
Published: April 2003

The aim of this study was to determine the prevalences and regional risk factors for respiratory symptoms in European and Californian farmers.

Farmers participating in the 1993–1997 surveys performed in Europe (n=7,188) and California (n=1,839) were included in this cross-sectional study. Respiratory symptoms and farming characteristics were assessed by questionnaire and risk factors associated with symptoms using logistic regression.

The prevalences of rhinitis and asthma were lower in European (12.7% and 2.8%) than in Californian farmers (23.9% and 4.7%), but chronic bronchitis and toxic pneumonitis were more prevalent in Europe (10.7% and 12.2%) than in California (4.4% and 2.7%). Respiratory symptoms were associated with poultry and rabbit farming, flower growing and the cultivation of grain and oil plants. Working in Europe was a statistically significant risk factor for chronic bronchitis and toxic pneumonitis. Chronic bronchitis was related to toxic pneumonitis, work inside confinement buildings and greenhouses.

Chronic bronchitis and toxic pneumonitis are highly prevalent among European farmers and are mainly attributable to indoor work.
Tularaemia
Authors: Tärnvik A. , Berglund L.
Published: April 2003

Tularaemia is a zoonotic bacterial disease of the Northern hemisphere. The causative agent,Francisella tularensis, is spread to humans by direct contact with infected rodents or lagomorphs, aerogenic exposure, ingestion of contaminated food or water, or by arthropod bites. The prevalence of tularaemia shows a wide geographic variation. In some endemic regions, outbreaks occur frequently, whereas nearby rural parts of a country may be completely free.

F. tularensisis a facultative intracellular pathogen and its primary mammalian target cell is the mononuclear phagocyte. When tularaemia is acquiredviathe skin, a primary ulcer is often detected and in general, regional lymph nodes become prominently enlarged. When contracted by inhalation, the disease may present with pneumonia. Nearly as frequent, however, is the development of fever and general illness with no respiratory symptoms and no pulmonary radiological changes. When present, the changes vary widely and may sometimes include hilar enlargement indistinguishable from that of lymphoma.

Within an outbreak, the first case of tularaemia is not always readily diagnosed. A decade may have lapsed since the disease was encountered and its existence may be more or less forgotten. The difficulty refers especially to the respiratory form, in which symptoms are less specific. In cases of atypical pneumonia or acute febrile disease with no local symptoms, a history of exposure to hares or rodents or merely living in an endemic region should be sufficient to include tularaemia among differential diagnoses.

The microbiological diagnosis of tularaemia relies mainly on serology, and the treatment on broad-spectrum antibiotics. For decades, a live vaccine has been successfully used in risk groups but is presently not available due to difficulties in standardisation.
Mould exposure at home relates to inflammatory markers in blood
Authors: Beijer L. , Thorn J. , Rylander R.
Published: April 2003

Living in damp buildings has been associated with airway symptoms, suspected to be due to inflammatory reactions. The relationship between home exposure to mould and signs of inflammation was, therefore, studied.

Nonsmoking subjects with a high (G-high, >4.0 ng·m−3, n=17) or low (G-low, <2.0 ng·m−3, n=18) amount of airborne β(1→3)-d-glucan, an indicator of mould biomass, in the home were recruited. Blood samples were analysed for granulocytic enzymes, T-cell subsets and the secretion of cytokines fromin vitroincubated peripheral blood mononuclear cells (PBMCs).

In the G-high group, the proportion of cytotoxic T-cells (CD8+S6F1+) was lower and secretion of tumour necrosis factor-α from PBMCs higher than in the G-low group. There were no significant differences in secretion of interferon gamma and interleukin (IL)-4 from PBMCs between the two groups. Among nonatopic subjects, the ratio between interferon gamma and IL-4 was significantly higher in the G-high group than in the G-low group and was related to the amount of β(1→3)-d-glucan in the home. No significant differences were found regarding secretion of IL-10 or IL-1β from PBMCs, eosinophil cationic protein or myeloperoxidase in serum, or differential cell counts in blood.

The effects found on inflammatory markers in relation to β(1→3)-d-glucan in the home suggest upregulation of some parts of the inflammatory/immunological system due to mould exposure.
Apoptosis of bronchoalveolar lavage lymphocytes in hypersensitivity pneumonitis
Authors: Laflamme C. , Israël-Assayag E. , Cormier Y.
Published: April 2003

The aim of this study was to look at the apoptosis of alveolar lymphocytes in hypersensitivity pneumonitis (HP). HP patients and normal unexposed controls were studied.

The percentage of apoptotic lymphocytes was significantly lower in HP patients than in normal patients (37.4±3.4versus56.5±5.5% for Annexin V and propidium iodine detection methods and 0.4±0.1versus1.0±0.2% for dUTP nick end-labelling technique (TUNEL)). The proportion of bronchoalveolar lavage (BAL) lymphocytes positive for Fas antigen was significantly higher in HP patients than in normal subjects (71.7±5.4versus50.4±9.0%). However, no significant difference was found in the proportion of BAL lymphocytes positive for Fas ligand (FasL) between the two groups. Soluble Fas (sFas) levels in the BAL fluid of the patients and normals were 80.5±8.5 pg·mL−1and 23.2±3.1 pg·mL−1, respectively. A positive correlation was found between the percentage of BAL lymphocytes and the levels of sFas for the total subjects but not within the separate study groups. The intracellular quantity of the inducible anti-apoptotic gene Bcl-xL product was significantly higher in the pulmonary lymphocytes of HP patients than in lymphocytes of the control, while no difference was found for constitutive anti-apoptotic protein (Bcl–2).

In conclusion, the apoptosis of pulmonary lymphocytes is lower in hypersensitivity pneumonitis than in normal subjects. This could be explained, at least in part, by an increase of soluble Fas, the anti-apoptic gene, and Bcl-xL.
Hypertonic saline increases secretory and exudative responsiveness of human nasal airwayin vivo
Authors: Greiff L. , Andersson M. , Wollmer P. , Persson C.G.A.
Published: April 2003

Hypertonic saline (HS) is used in sputum induction studies. However, little is known about the physiological effects of HS on human airwaysin vivo. The present study takes advantage of the fact that the airway effects of topical challenges may be accurately examined in the readily accessible nasal airway. The present study specifically examines whether exposure to HS affects histamine challenge-induced exudation of plasma (α2-macroglobulin) and methacholine-induced secretion of mucin (fucose).

Isotonic saline and HS (27 and 45 g·L−1), with and without concomitant histamine challenges, and with and without preceding methacholine challenges, were administered onto the nasal mucosa in 16 healthy subjects. Lavage fluid levels of α2-macroglobulin and fucose were analysed.

Histamine produced a significant mucosal output of plasma (α2-macroglobulin). HS itself did not evoke exudation of α2-macroglobulin, but it significantly increased the plasma exudation effect of histamine. Methacholine produced a significant nasal mucosal output of fucose. HS also increased the mucin secretion (fucose), and it enhanced the secretory effect of methacholine.

The authors concluded that hypertonic saline alone evokes mucinous secretion in human nasal airwaysin vivoand that it also enhances the exudative and secretory effects of histamine and methacholine, respectively. Through different mechanisms the HS exposure may also improve the recovery of soluble indices in human nasal airways. Whether or not the present findings are translatable to human bronchial airways remains to be examined.
High Mallampati score and nasal obstruction are associated risk factors for obstructive sleep apnoea
Authors: Liistro G. , Rombaux Ph. , Belge C. , Dury M. , Aubert G. , Rodenstein D.O.
Published: April 2003

Induced nasal obstruction can cause obstructive apnoeas in healthy subjects during sleep, but the relationship between nasal resistance measured during wakefulness and obstructive sleep apnoea syndrome (OSAS) is weak. It was postulated that if the subjects could not breathe through the nose, the oral airway must be used, but if this airway is narrowed as well, then it could precipitate sleep-disordered breathing (SDB).

Nasal patency, Mallampati score (MS), neck circumference and body mass index were measured in 202 subjects referred to the authors' hospital to undergo a full-night polysomnography for suspicion of SDB.

A significant correlation was found between the MS and apnoea/hypopnoea index measured during sleep. However, the relationship between these parameters was only significant in patients with nasal obstruction. The relative risk of having OSAS with a MS of III or IV was 1.95 for the whole group and 2.45 in patients with nasal obstruction.

In conclusion, a high Mallampati score represents a predisposing factor for obstructive sleep apnoea syndrome, especially if it is associated with nasal obstruction. These patients merit special attention from both the sleep physician and the anaesthetist.
Evaluation of a portable device for diagnosing the sleep apnoea/hypopnoea syndrome
Authors: Dingli K. , Coleman E.L. , Vennelle M. , Finch S.P. , Wraith P.K. , Mackay T.W. , Douglas N.J.
Published: April 2003

Waiting times for hospital-based monitoring of the obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are rising. This study tested whether Embletta, a new portable device, may accurately diagnose OSAHS at home.

A synchronous comparison to polysomnography was performed in 40 patients and a comparison of home Embletta studies with in-laboratory polysomnography was performed in 61 patients.

In the synchronous study, the mean difference (polysomnography–Embletta) in apnoeas+hypopnoeas (A+H)·h−1in bed was 2·h−1. In comparison to the apnoea/hypopnoea index (AHI)·h−1slept, the Embletta (A+H)·h−1in bed differed by 8·h−1. These data were used to construct diagnostic categories in symptomatic patients from their Embletta results: “OSAHS” (≥20 (A+H)·h−1in bed), “possible OSAHS” (10–20 (A+H)·h−1in bed) or “not OSAHS” (<10 (A+H)·h−1in bed). In the home study, the mean difference in (A+H)·h−1in bed was 3·h−1. In comparison to the polysomnographic AHI·h−1slept, the Embletta (A+H)·h−1in bed differed by 6±14·h−1. Using the above classification, all nine patients categorised as not OSAHS had AHI <15·h−1slept on polysomnography and all 23 with OSAHS on Embletta had an AHI ≥15 on polysomnography, but 18 patients fell into the possible OSAHS category potentially requiring further investigation and 11 home studies failed.

Most patients were satisfactorily classified by home Embletta studies but 29 out of 61 required further investigation. The study suggested a 42% saving in diagnostic costs over polysomnography if this approach were adopted.
Systemic effects of chronic obstructive pulmonary disease
Authors: Agustí A.G.N. , Noguera A. , Sauleda J. , Sala E. , Pons J. , Busquets X.
Published: April 2003

Chronic obstructive pulmonary disease (COPD) is characterised by an inappropriate/excessive inflammatory response of the lungs to respiratory pollutants, mainly tobacco smoking.

Recently, besides the typical pulmonary pathology of COPD (i.e.chronic bronchitis and emphysema), several effects occurring outside the lungs have been described, the so-called systemic effects of COPD. These effects are clinically relevant because they modify and can help in the classification and management of the disease.

The present review discusses the following systemic effects of chronic obstructive pulmonary disease: 1) systemic inflammation; 2) nutritional abnormalities and weight loss; 3) skeletal muscle dysfunction; and 4) other potential systemic effects. For each of these, the potential mechanisms and clinical implications are discussed and areas requiring further research are highlighted.
The nonhospital costs of care of patients with CF in The Netherlands: results of a questionnaire
Authors: Wildhagen MF , Verheij JB , Verzijl JG , Gerritsen J , Bakker W , Hilderink HB , ten Kate LP , Tijmstra T , Kooij L , Habbema JD
Published: April 2003

Cystic fibrosis (CF) causes a relatively high medical consumption. A large part of the treatment takes place at home. Because data regarding nonhospital care are lacking, we wished to determine the costs of care of patients with CF outside the hospital. A questionnaire was sent to 73 patients with CF from two Dutch hospitals (response rate 64%, 14 children and 33 adults). Average consumption and average costs per patient per year were calculated for children and adults for six categories: nonhospital medical care; domestic help; diet; travelling because of CF; medication; and devices and special facilities at home, work or school. The average nonhospital costs of care amounted to Pounds 4,641 per child per year (range Pounds 712-13,269) and Pounds 10,242 per adult (range Pounds 1,653-26,571). Nonhospital medical care for children and adults accounted for, respectively, 8 and 5% of these costs, domestic help for 15 and 9%, diet for 10 and 7%, travelling because of CF for 4 and 8%, medication for 63 and 67%, and devices and special facilities at home, work or school for 1 and 4%. Nonhospital costs of care of cystic fibrosis are very high and amount to 50% of the total (medical and nonmedical) lifetime costs of cystic fibrosis.
Capsaicin cough receptor sensitivity test in children
Authors: Chang AB , Phelan PD , Roberts RG , Robertson CF
Published: April 2003

Capsaicin has been used as a tussive agent in studies in adults to determine cough receptor sensitivity. The aim of this study was to determine the tolerance, repeatability and influence of inspiratory flow on the capsaicin cough receptor sensitivity test in children. Thirty children (mean age 11 yrs; range 6-16 yrs) were tested on two different days, to determine the lowest concentration of capsaicin required to stimulate two or more coughs (cough threshold (Cth)), 2-4 coughs (C2), and five or more coughs (C5). Capsaicin was nebulized through a dosimeter, with an arrangement that allowed the subjects to visualize and regulate their inspiratory flow. Using a constant inspiratory flow of 20 L x min(-1), tests were reproducible for C2, C5 and Cth (doubling dose changes of 1.13, 1.03 and 1.08, respectively). An increase in the inspiratory flow from 20 to 60 L x min(-1) significantly increased C2 (19.5 to 46.8 microM; p=0.016) and C5 (46.8 to 128.8 microM; p=0.008). We conclude that in children, the capsaicin cough challenge test: 1) is well-tolerated; 2) is highly repeatable; and that 3) the inspiratory flow significantly influences cough receptor sensitivity and repeatability of the test and should, thus, be regulated.
Expression of CD44 and integrins in bronchial mucosa of normal and mildly asthmatic subjects
Authors: Peroni DG , Djukanovic R , Bradding P , Feather IH , Montefort S , Howarth PH , Jones DB , Holgate ST
Published: April 2003

We have investigated the expression of cell surface markers and leucocyte cell adhesion molecules by immunohistochemistry in bronchial biopsies from 10 mild atopic asthmatics and 8 normal, nonatopic subjects. Significantly increased numbers of eosinophils (p<0.01) were evident in the bronchial submucosa of asthmatic subjects. In epithelium there were more CD44+ (p<0.02) and lymphocyte function-associated antigen-1 (LFA-1)+ (p<0.06) leucocytes in asthmatics than in normal subjects. Bronchial epithelial cells stained positively with anti-CD44 monoclonal antibodies (moAb) in both groups; however, when the staining was expressed as percentage of the total basement membrane, a considerable and highly significant increase was observed in the asthmatics (median 80 vs 22%, p=0.003). Few leucocytes were positive for very late activation antigen (VLA)-1, VLA-2 and VLA-4. The moAb for VLA-6 stained the basement membrane of the bronchial epithelium; while intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were constitutively expressed in endothelium. A positive correlation was found between LFA-1+ cells and activated eosinophils (EG2+) in the submucosa (p<0.005; r(s)=0.80). We conclude that even in mild asthma there is evidence of increased expression of cell surface ligands, and suggest that adhesive mechanisms play a role both in cell recruitment and disease activity.
Experimental rhinovirus infection in volunteers
Authors: Bardin PG , Sanderson G , Robinson BS , Holgate ST , Tyrrell DA
Published: April 2003

Experimental viral disease studies in volunteers have clarified many aspects of the pathogenesis of human viral disease. Recently, interest has focused on rhinovirus-associated asthma exacerbations, and new volunteer studies have suggested that airway responsiveness (AR) is enhanced during a cold. For scientific, ethical and safety reasons, it is important to use validated methods for the preparation of a virus inoculum and that the particular virological characteristics and host responses should not be altered. We have prepared a new human rhinovirus (HRV) inoculum using recent guidelines and assessed whether disease characteristics (for example, severity of colds or changes in AR) were retained. Studies were conducted in 25 clinically healthy volunteers using a validated HRV inoculum in the first 17 and a new inoculum in the subsequent eight subjects. Severity of cold symptoms, nasal wash albumin levels and airway responsiveness were measured, and the new inoculum was prepared from nasal washes obtained during the cold. The new inoculum was tested using standard virological and serological techniques, as well as a polymerase chain reaction for Mycoplasma pneumoniae. No contaminating viruses or organisms were detected and the methods suggested were workable. Good clinical colds developed in 20 of the 25 subjects and median symptom scores were similar in the validated and new inoculum groups (18 and 17.5, respectively; p=0.19). All subjects shed virus, and there were no differences noted in viral culture scores, nasal wash albumin and rates of seroconversion in the two groups. Although airway responsiveness increased in both groups (p=0.02 and p=0.05), the degree of change was similar. We have performed experimental rhinovirus infection studies and demonstrated similar clinical disease in two inoculum groups. Amplified airway responsiveness was induced; continuing studies will define the mechanisms and suggest modes of treatment.
Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics
Authors: Overbeek SE , Rijnbeek PR , Vons C , Mulder PG , Hoogsteden HC , Bogaard JM
Published: April 2003

Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) = sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 microg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg x mL(-1). MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters. In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log, EC50 were not significantly different between the groups. We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.
Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro
Authors: Pype JL , Dupont LJ , Demedts MG , Verleden GM
Published: April 2003

(D-ALa2, NMePhe4, Gly-ol5) encephalin (DAMGO), a selective mu-opioid receptor agonist, has previously been demonstrated to inhibit the cholinergic and the noncholinergic contraction in guinea-pig airways. In contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea when stimulated at 8 Hz. We investigated whether DAMGO, a selective mu-opioid receptor agonist, [D-Pen 2,5] encephalin (DPDPE), a selective delta-opioid receptor agonist, and U-69593, a selective kappa-opioid receptor agonist could modulate the cholinergic contraction in the upper trachea at different frequencies of stimulation. Moreover, we have investigated whether DAMGO, DPDPE and U-69593 could also modulate the iNANC relaxation. DAMGO (1-100 microM) inhibited the cholinergic contraction in the upper trachea with a maximum inhibition of 57+/-15% at 1 Hz (n=4; p<0.05). On the other hand, DPDPE (10 microM) and U69593 (10 microM) did not produce any significant inhibition of the cholinergic contraction. Naloxone, an opioid receptor antagonist (100 microM), was able to antagonize the inhibitory effect of DAMGO (n=5; p<0.01) on the cholinergic contraction at a frequency of 2 Hz. DAMGO (10 microM) did not displace the cumulative concentration-response relationship to acetylcholine (10 nM-10 mM), (n=4; NS). This provides evidence that prejunctional mu-opioid receptors (and not delta-opioid or kappa-opioid receptors) modulate cholinergic contraction in the upper trachea. In contrast, DAMGO (10 microM) had no significant inhibitory effect on the nonadrenergic relaxation (n=4; NS) in the upper trachea. Neither DPDPE nor U-69593 had any effect on the nonadrenergic relaxation. These findings suggest that DAMGO directly inhibits the cholinergic contraction and that the opioid receptor involved in the inhibition of the cholinergic contraction in the upper trachea is of the mu-opioid type. The finding that opioids inhibit cholinergic contraction without altering NANC relaxations suggests that distinct populations of nerves mediate these two effects.
Isotonic smooth muscle response in human bronchi exposed in vitro to nitrogen dioxide
Authors: Chitano P , Lucchini RE , Calabro F , Saetta M , Maestrelli P , Fabbri LM , Mapp CE
Published: April 2003

Exposure to nitrogen dioxide (NO2), a common oxidant airborne pollutant, has been shown to cause reversible effects on lung function and airway responsiveness, in addition to airways inflammation. However, there have been conflicting reports concerning NO2-induced airway hyperresponsiveness. In the present study, we investigated the isotonic smooth muscle response in isolated human bronchi previously exposed in vitro to NO2. Bronchial segments were obtained from 12 patients who had undergone thoracotomy for lung cancer. Bronchial segments from each patient were exposed to air and to 2.5 parts per million (ppm) NO2 for 4 h. The contractile response of bronchial rings to acetylcholine, neurokinin A (NKA), and substance P was then studied under isotonic conditions. The response to NKA was also studied in rings, with or without epithelium, exposed either to air or 7 ppm NO2. No NO2-induced alteration of the bronchial smooth muscle isotonic response was found under any of the experimental conditions. We conclude that in vitro exposure to up to 7 ppm nitrogen dioxide does not cause alterations of the human bronchial smooth muscle shortening capacity.
Ozone-induced mediator release from human bronchial epithelial cells in vitro and the influence of nedocromil sodium
Authors: Rusznak C , Devalia JL , Sapsford RJ , Davies RJ
Published: April 2003

Although animal and human studies have demonstrated that ozone inhalation leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epithelial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion molecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA). O3 exposure led to significant epithelial cell damage at concentrations of 10-500 ppb O3, as indicated by increased release of [51Cr]-labelled sodium chromate. At concentrations of 10-100 ppb, O3 induced maximal release of interleukin-8 (IL-8), granulocyte/macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and sICAM-1. The IL-8 and GM-CSF release increased significantly from 5.64+/-0.58 and 0.04+/-0.03 pg x microg(-1) cellular protein, respectively, from control cells exposed to air, to 20.16+/-2.56 and 0.20+/-0.04 pg x microg(-1) cellular protein, respectively, from cells exposed to 50 ppb O3. 10(-5) M nedocromil sodium significantly attenuated the O3-induced release of both IL-8 and GM-CSF (p<0.01). The TNF-alpha and sICAM-1 increases after exposure to 10-50 ppb O3, were also abrogated by treatment of the cells with 10(-5) M nedocromil sodium (p<0.05). Similarly, the antioxidant, glutathione, at concentrations of 400-600 microM, significantly reduced the O3-induced release of IL-8 (p<0.05). In conclusion, these studies indicate that ambient concentrations of ozone may induce airway inflammation, through release of proinflammatory mediators from airway epithelial cells. This effect may be inhibited both by the anti-inflammatory drug, nedocromil sodium, and the naturally occurring antioxidant glutathione.
Adherence to guidelines for the prevention of HIV-related respiratory diseases
Authors: Montaner JS , Phillips P , Zala C , Craib KJ , O'Shaughnessy MV , Schechter MT
Published: April 2003

In this study we characterized the pattern of use of preventive therapies for specific respiratory diseases within a cohort of homosexual men and assessed the impact of targeted feedback on the level of compliance with guidelines for these diseases. All human immunodeficiency virus seronegative (HIV-) (n=169) and acquired immune deficiency syndrome (AIDS)-free human immunodeficiency virus seropositive (HIV+) (n=154) participants in our cohort, who completed four annual visits between October 1989 and December 1993, were identified. Information about the use of purified protein derivative (PPD) (tuberculin) testing, history of pneumococcal vaccinations, influenza vaccinations, use of Pneumocystis carinii pneumonia (PCP) prophylaxis, symptoms and CD4 counts was obtained yearly for each subject. In 1992, participating physicians were provided with feedback regarding the overall levels of compliance with contemporary guidelines for the prevention of respiratory disease. As part of this exercise, the guidelines were distributed and discussed. The percentage of HIV+ patients who underwent PPD testing increased from 43 to 65% during the study (p=0.001). Significantly more HIV+ than HIV- patients underwent PPD testing (p<0.001). A total of 144 (94%) HIV+ men received at least one influenza vaccination compared to 60 (35%) HIV- men (p<0.001). Utilization of influenza vaccination in the HIV+ group significantly increased from 78% in 1992 to 92% in 1993 (p<0.001). A total of 104 (68%) HIV+ men received pneumococcal vaccination compared to 2 (1%) HIV- men (p<0.001). Among HIV+ individuals whose absolute CD4+ count was less than 200 cells x mm(-3), the percentage of men who received primary PCP prophylaxis was 0, 86, 72 and 88 for the years 1990-1993, respectively. Among HIV+ patients whose only eligibility criterion for PCP prophylaxis was a CD4+ percentage <20%, compliance was 55, 30, 37 and 50% for the years 1990-1993, respectively. Among HIV+ subjects, increases in the compliance level were noted for all preventive therapies after targeted feedback was provided during the last quarter of 1992. However, only utilization of influenza vaccine exceeded a 90% compliance in 1993. These data demonstrate that a suboptimal level of compliance with current guidelines for the prevention of respiratory disease among human immunodeficiency virus-infected individuals can be significantly improved using targeted feedback. Although it is likely that similar effects could be achieved in other populations or the community at large, this remains to be demonstrated.
Effect of upper airway cooling and CO2 on diaphragm and geniohyoid muscle activity in the rat
Authors: O'Halloran KD , Curran AK , Bradford A
Published: April 2003

Upper airway (UA) reflexes play an important role in regulating breathing and UA patency, but the effects of UA CO2 and cooling on ventilation and UA muscle activity are controversial. Diaphragm and geniohyoid electromyographic activities were recorded in anaesthetized rats, breathing spontaneously through a low-cervical tracheostomy. Warmed, humidified air containing 0 or 10% CO2 and cooled, room humidity air were applied at constant flow to the UA through a high- cervical tracheostomy. Spontaneous tracheal airflow, UA airflow and temperature, blood pressure, and rectal temperature were recorded. In all animals, the geniohyoid muscle had phasic inspiratory activity, which slightly preceded diaphragmatic activity. CO2 had no effect on mean peak integrated diaphragmatic activity and variable effects on geniohyoid activity. The coefficients of variation of these activities were unaffected by CO2. Similar results were obtained following bilateral mid-cervical vagotomy. Cool air decreased respiratory frequency (78+/-8%) (mean+/-SD % of control), peak inspiratory flow (78+/-5%) and diaphragmatic activity (77+/-4%), and increased geniohyoid activity (149+/-11%). Cutting the superior laryngeal nerves abolished these effects. In conclusion, whilst moderate upper airway cooling inhibits breathing and excites geniohyoid muscle activity, upper airway carbon dioxide has minimal effect.
Does spontaneous respiration alter pulmonary artery input impedance?
Authors: Castiglioni P , Di Rienzo M , Grossoni M , Tommasini R , Morpurgo M
Published: April 2003

The aim of this study was to determine whether spontaneous respiration influences pulmonary artery input impedance, a question that has received little attention in the literature. Impedance values were assessed during three different phases of the respiratory cycle, namely inspiration, expiration and postexpiration (i.e. the null respiratory flow period between expiration and the next inspiration) in five anaesthetized spontaneously breathing dogs. Firstly, impedance values during postexpiration were taken as the reference baseline, and compared with values obtained during inspiration and expiration. Then, differences between values in inspiration and in expiration were tested, taking impedance during inspiration as the baseline. Differences with respect to postexpiration were found for three parameters of input impedance: input resistance, characteristic impedance, and the frequency at the first zero-crossing of the impedance phase from negative to positive values (f(cross)). Input resistance was significantly lower in inspiration (85% of the baseline), characteristic impedance was significantly greater in inspiration and in expiration (112 and 119% respectively), and f(cross) was significantly lower in expiration (89%). By contrast, only input resistance differed significantly when inspiration was compared to expiration. Therefore, spontaneous respiration was shown to influence input impedance significantly. The observed changes in characteristic impedance and f(cross) might be explained by a stiffening of the pulmonary artery wall, due to neural and/or mechanical factors, during inspiration and expiration.
Relationship between breathlessness and hypoxic and hypercapnic ventilatory response in patients with COPD
Authors: Kobayashi S , Nishimura M , Yamomoto M , Akiyama Y , Miyamoto K , Kawamaki Y
Published: April 2003

The purpose of this study is to examine the relationship between breathlessness and the ventilatory response to hypercapnia or hypoxia in patients with chronic obstructive pulmonary disease (COPD). Fifteen male patients (mean forced expiratory volume in one second (FEV1): 1.13 L) underwent tests to determine hyperoxic hypercapnic ventilatory response (HCVR) and isocapnic hypoxic ventilatory response (HVR) with simultaneous quantification of breathlessness by modified Borg scale. The ventilatory output was evaluated by the ratio of minute ventilation (V'E) divided by measured maximal voluntary ventilation (MVV). The magnitude of HCVR or HVR was assessed as the slope value of the V'E/MVV-end-tidal carbon dioxide pressure (PET,CO2) or arterial oxygen saturation (Sa,O2) regression line, respectively. The breathlessness during the tests was evaluated not only linearly in relation to V'E/MVV, but also at given levels of PET,CO2 or Sa,O2. The mean value of the breathlessness at two different levels of ventilation was greater during HVR than during HCVR, suggesting that hypoxia is dyspnogenic independently of ventilatory stimulation. The HCVR was inversely correlated with the breathlessness response to ventilation, while similar correlation was partly present for HVR. The HVR was positively correlated with the breathlessness at an Sa,O2 of 80%, whilst there was no such correlation between the HCVR and the breathlessness related to PET,CO2. Therefore, patients with a higher breathlessness related to increased ventilation had a lower HCVR and HVR, whilst those with a higher breathlessness with desaturation, which might include a direct influence of hypoxia, had a higher HVR. These findings suggest an interaction between ventilatory response and breathlessness during the test, which may partly include behavioural modulation of HCVR and HVR through the breathlessness in various ways, depending on the origin and nature of the sensation.