bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in abdominal and neck circumferences in patients with and without obstructive sleep apnoea
Authors: Hoffstein V , Mateika S
Published: November 2022

We have recently shown that patients with sleep apnoea have thicker necks than non-apnoeic snoring controls. However, it was not clear whether this difference simply reflects the fact that apnoeic patients are more obese than the non-apnoeic ones, or whether it represents a preferential distribution of fat over the neck region compared to the abnormal region. We therefore measured the neck and abdominal circumferences in a large group of 670 patients suspected of having sleep apnoea, all of whom had full nocturnal polysomnography, including measurement of snoring. We divided these patients into apnoeic and non-apnoeic groups based on the apnoea/hypopnoea index (AHI) of 10. Apnoeic patients had significantly higher body mass index (BMI), neck, and abdominal circumferences than non-apnoeic controls. We then matched apnoeic and non-apnoeic patients exactly, one-for-one for BMI and age; this procedure left us with 156 patients in each group. Abdominal circumferences were similar, but the neck circumference was significantly higher in apnoeic patients (41.2 +/- 3.5 cm vs 39.1 +/- 3.7 cm, p less than 0.0001). Multiple stepwise linear regression analysis revealed that neck circumference and BMI correlated significantly with apnoea (multiple R2 = 0.27, p less than 0.001) and snoring (multiple R2 = 0.19, p less than 0.001). We conclude that obese patients with sleep apnoea have fatter necks than equally obese non-apnoeic snorers, and that the neck circumference could be a significant determinant of apnoea and snoring.
Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat
Authors: Hernnas J , Nettelbladt O , Bjermer L , Sarnstrand B , Malmstrom A , Hallgren R
Published: November 2022

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.
Assessing physiological benefit from domiciliary nebulized bronchodilators in severe airflow limitation
Authors: Morrison JF , Jones PC , Muers MF
Published: November 2022

In steroid resistant chronic obstructive pulmonary disease (COPD) we assessed the effect of q.i.d. domiciliary nebulized fenoterol (F) 1.25 mg and ipratropium (I) 0.5 mg for three weeks in a placebo-controlled, randomized, double-blind, crossover study. The twenty patients studied (mean forced expiratory volume in one second (FEV1) 0.8 l) all showed less than 20% increase in FEV1 to 200 micrograms inhaled salbutamol (S) and less than 20% increase in peak expiratory flow rate (PEFR) after 2 weeks prednisolone therapy. Respiratory function tests, 5 min walking distance (5 MWD), visual analogue scales (VAS) for breathlessness, oxygen cost diagrams and reversibilities were performed weekly for three weeks with patients on their usual therapy, after three weeks domiciliary F+I, after three weeks saline and, finally, after a further three weeks on usual therapy again. Primary end-points, selected prior to unblinding, were mean home twice daily PEFR, trapped gas volume, FEV1 and 5 MWD. Home PEFR rose from 164 l.min-1 on saline to 196 l.min-1 on F+I (p = 0.0001). Secondary end-point analysis revealed a fall in home inhaler usage and a rise in VAS. Using the criterion of +15% and greater than 20 l.min-1 increase in home PEFR, 11 out of 20 patients had a "positive" trial. We suggest that such patients, but not others, benefit from long-term, nebulized beta 2-agonist and ipratropium. Trials using home PEFR recordings should be used to identify them.
Screening of pulmonary hypertension in chronic obstructive pulmonary disease and silicosis by discriminant functions
Authors: Evers H , Liehs F , Harzbecker K , Wenzel D , Wilke A , Pielesch W , Schauer J , Nahrendorf W , Preisler J , Luther R , et al.
Published: November 2022

The aim of our prospective multicentric study was to develop a screening method for pulmonary hypertension in patients with chronic lung diseases. We investigated 710 patients in 10 hospitals: 315 males and 109 females with chronic obstructive pulmonary disease, and 286 males with silicosis. Manifest pulmonary hypertension was defined as pulmonary artery pressure greater than 20 mmHg (2.7 kPa) at rest. The multivariate statistical method used was a stepwise discriminant analysis. In males with chronic obstructive pulmonary disease, the diameter of the right descending pulmonary artery, forced expiratory volume in one second (FEV1) arterial oxygen tension (PaO2) at rest, and age turned out to be relevant for discrimination of groups with and without manifest pulmonary hypertension. For females the FEV1/FVC (forced vital capacity) ratio replaced the absolute value of FEV1 in the calculated discriminant function. In females, sensitivity and specificity were below 80%. In males, both were distinctly above 80%. In silicosis, the diameter of the right descending pulmonary artery was much less important, since it could frequently not be measured precisely. In these cases, precision of the prediction of about 80% could only be obtained by combined evaluation of spirometry, PaO2 during exercise, and body plethysmography. The calculated discriminant functions are appropriate for screening patients with risk of pulmonary hypertension. For different chronic lung diseases, and for both sexes, different combinations of parameters are relevant. The method is recommended to select patients who should undergo an invasive examination of pulmonary haemodynamics.
Population values of lung volumes and flows in children: effect of sex, body mass and respiratory conditions
Authors: Pistelli R , Brancato G , Forastiere F , Michelozzi P , Corbo GM , Agabiti N , Ciappi G , Perucci CA
Published: November 2022

The functional relationship of gender, anthropometric measures and respiratory condition in predicting respiratory function in children was explored, using data collected in a random sample survey in Central Italy (2,176 subjects). Regression equations for the logarithmic transformation of the functional data were obtained, using sex, ln(height), ln(body mass index) (BMI) and ln(age) as predicting variables. The fit of the model was better for forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) (R2 = 0.655, 0.603 and 0.312, respectively) than for maximal expiratory flows. Variables indicating the presence of respiratory conditions (recent respiratory infections, asthma, cough and/or phlegm) were forced in the models; only a marginal change in the predictions was observed. Data analysis while controlling for FVC, as a proxy for total lung capacity, revealed no substantial sex difference in airways; furthermore, airways size relative to lung size falls with increasing FVC in both sexes. In overweight subjects (BMI greater than 90th percentile) the relationship between height and lung volume was modified by sex, the coefficient for ln(height) being higher in girls and lower in boys. A comparison between equations from the present study and available reference data revealed that our population differs from standards derived from laboratory data and is more similar to those derived from population studies.
The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa
Authors: Baldwin DR , Wise R , Andrews JM , Ashby JP , Honeybourne D
Published: November 2022

The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage. Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling. The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage. In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations. Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection.
Bronchoalveolar disease in dyskeratosis congenita
Authors: Verra F , Kouzan S , Saiag P , Bignon J , de Cremoux H
Published: November 2022

Dyskeratosis congenita (DC) is an unusual familial disorder primarily affecting the skin and its appendages. We report the case of a DC patient with chronic respiratory tract involvement, confirming the features previously reported by a small number of authors: 1) chronic bronchoalveolar involvement is not unusual in this disorder; 2) the main features are early sputum production with subsequent bronchial and alveolar destruction; 3) after onset of dyspnoea the course is rapidly fatal, with progressive respiratory failure. Immune deficiency and repeated bronchoalveolar infections may be involved in the pathogenesis of these manifestations.
Vascular and cardiac reactivity in pulmonary hypertension due to chronic obstructive lung disease: assessment with various oxygen concentrations
Authors: Saadjian A , Philip-Joet F , Levy S , Arnaud A
Published: November 2022

The aim of the present work was to evaluate vasoreactivity in patients with pulmonary hypertension related to chronic obstructive lung disease. This was done by comparing haemodynamic data recorded while patients were breathing room air, and hypoxic and hyperoxic mixtures. We estimated the role of vasoconstriction in determining the level of pulmonary hypertension. This study included 26 patients with moderate pulmonary hypertension mean pulmonary arterial pressure (MPAP) = 27.3 +/- 1.2 mmHg) secondary to chronic obstructive lung disease (COLD), forced expiratory volume in one second (FEV1) = 0.95 +/- 0.13 l; arterial oxygen tension (PaO2) = 8.7 +/- 0.25 kPa). After insertion of a thermodilution catheter in the pulmonary artery and a cannula in the femoral artery, mixtures containing 15, 21, 30 and 100% oxygen were randomly administered for 20 min each. As fractional inspiratory oxygen (FIO2) increased, MPAP decreased relatively less than cardiac index. Cardiac output was at its highest during room air breathing and the hypoxic mixture did not lead to a further increase. Unlike normal subjects, in whom adjustment of cardiac output is achieved by heart rate alone, haemodynamic regulation in these patients also involved stroke volume. Variations in MPAP and cardiac index were strongly correlated with arterial oxygen saturation (SaO2). The greatest variations were noted in the patients with the highest pulmonary hypertension. Under normoxic and hyperoxic condition the relationship between pulmonary artery driving pressure and cardiac index was linear and its slope steeper in patients having the highest pulmonary hypertension at steady-state.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls
Authors: Djukanovic R , Lai CK , Wilson JW , Britten KM , Wilson SJ , Roche WR , Howarth PH , Holgate ST
Published: November 2022

We studied the role of atopy, as defined by positive skin tests to common inhalant allergens, in allergic bronchial inflammation. Endobronchial biopsies were taken via the fibreoptic bronchoscope in 13 symptomatic atopic asthmatics, 10 atopic nonasthmatics, and 7 normals. The numbers of mast cells, identified in the submucosa by immunohistochemistry using the AA1 monoclonal antibody against tryptase, were no different between the three groups, but electron microscopy showed that mast cell degranulation, although less marked in atopic nonasthmatics, was a feature of atopy in general. The numbers of eosinophils, identified by immunohistochemical staining using the monoclonal anti-eosinophil cationic protein antibody, EG2, were greatest in the asthmatics, low or absent in the normals and intermediate in the atopic nonasthmatics. In both atopic groups eosinophils showed ultrastructural features of degranulation. Measurements of subepithelial basement membrane thickness on electron micrographs showed that the collagen layer was thickest in the asthmatics, intermediate in the atopic nonasthmatics and thinnest in the normals. The results suggest that airways eosinophilia and degranulation of eosinophils and mast cells, as well as increased subepithelial collagen deposition, are a feature of atopy in general and suggest that the degree of change may determine the clinical expression of this immune disorder.
The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro
Authors: Feldman C , Read R , Rutman A , Jeffery PK , Brain A , Lund V , Mitchell TJ , Andrew PW , Boulnois GJ , Todd HC , et al.
Published: November 2022

The interaction of Streptococcus pneumoniae with human ciliated upper respiratory mucosa was studied in an agar-embedded organ culture of nasal turbinate tissue, which only exposed the intact epithelial surface and its secretion. The ciliary beat frequency, measured along the edge of the organ culture, was slowed by 13% in the presence of S. pneumoniae after 16 h (p less than 0.05) compared with the control, and by 24% after 24 h (p less than 0.01). Light microscopy showed bacteria in a thickened gelatinous layer, which obscured the surface of the organ culture. Transmission and scanning electron microscopy confirmed the association of bacteria with the gelatinous layer above an epithelial surface which showed only minor changes compared to uninfected control organ cultures. Contact between bacteria and normal or damaged epithelial cells was not seen. S. pneumoniae in organ culture developed projections from their surface, which were not present after broth culture. S. pneumoniae interactions with epithelial-derived secretions, the formation of a thickened gelatinous layer, and the effects of bacterial toxins on ciliary motility, may be important during colonization of the respiratory tract.
Trichosporon beigelii pneumonitis following busulphan-induced leucopenia
Authors: Yamauchi K , Sato T
Published: November 2022

We present a 41 yr old male, who died of respiratory failure due to infiltration of Trichosporon beigelii (cutaneum) into the pulmonary interstitial spaces with systemic dissemination. Busulphan-induced leucopenia in the chronic phase of chronic myelogenous leukaemia had progressed before this infection developed. In leukaemic patients with profound leucopenia, interstitial pneumonitis due to T. beigelii should be considered as a possible cause of otherwise unexplained hypoxaemia.
Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease
Authors: Hay JG , Stone P , Carter J , Church S , Eyre-Brook A , Pearson MG , Woodcock AA , Calverley PM
Published: November 2022

Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.
Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage
Authors: Spiteri MA , Clarke SW , Poulter LW
Published: November 2022

Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease.
Pulmonary function in childhood connective tissue diseases
Authors: Cerveri I , Bruschi C , Ravelli A , Zoia MC , Fanfulla F , Zonta L , Pellegrini G , Martini A
Published: November 2022

The term connective tissue diseases (CTD) defines a group of illnesses characterized by the presence of immune abnormalities and by widespread inflammation involving various organs and tissues including the lung. These diseases are not frequent in the paediatric age group. Very few data on pulmonary function are available in paediatric CTD. We investigated possible early lung function abnormalities and any likely relationship with clinical activity of the disease in a group of 81 paediatric CTD patients, without clinical or radiological evidence of pulmonary involvement. Measurement of lung volumes and diffusion lung capacity were performed. A sample of 65 subjects, defined as normal on the basis of history and clinical examination, and matched by age and height with the group of patients, was chosen as control group. CTD patients did not show significant deviations from the control distribution with respect to functional residual capacity (FRC) and maximal expiratory flow at 75% of the forced vital capacity (MEF75) values. On the contrary, both vital capacity (VC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were quite impaired in most CTD during the active phase of the disease. Our results show a functional lung impairment in most children with clinically active CTD, even in absence of abnormalities on chest X-ray pictures.
Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking
Authors: Bjermer L , Hallgren R , Nilsson K , Franzen L , Sandstrom T , Sarnstrand B , Henriksson R
Published: November 2022

Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects.
Reproducibility of childhood respiratory symptom questions
Authors: Brunekreef B , Groot B , Rijcken B , Hoek G , Steenbekkers A , de Boer A
Published: November 2022

The reproducibility of answers to childhood respiratory symptom questions was investigated by administering two childhood respiratory symptom questionnaires twice, with a one month interval, to the same population of Dutch school children. The questionnaires were completed by the parents of 410 children from 6-12 yrs old. One questionnaire was developed by the World Health Organization (WHO). The other questionnaire was developed for use by school health services and was based mainly on the American Thoracic Society (ATS) questionnaire for respiratory symptoms in childhood. It was called the Child Health Care (CHC) Questionnaire. Half of the parents received a questionnaire in which the WHO questions came first on both occasions, the other half a questionnaire in which the CHC questionnaire came first on both occasions. The reproducibility of the answers was assessed by calculating Cohen's Kappa, a chance-corrected measure of association. Questions about "wheeze", "asthma", "bronchitis", "cough and phlegm", and "pneumonia" were found to give good to excellent reproducibility, with Kappa values ranging from 0.60-0.96. Questions about "phlegm", "cough", "chest congestion" and "runny/congested nose" were less satisfactory in this respect, with Kappa values generally well below 0.60. The reproducibility of the answers did not depend on the order in which the questionnaires were administered, on the gender or age of the child, or on the smoking habits or educational level of the parents.
A comparison of six different ways of expressing the bronchodilating response in asthma and COPD; reproducibility and dependence of prebronchodilator FEV1
Authors: Dompeling E , van Schayck CP , Molema J , Akkermans R , Folgering H , van Grunsven PM , van Weel C
Published: November 2022

Various indices are used to express the bronchodilating response. It is unclear, however, which index is most informative. The aim of this study was to compare six expressions of the bronchodilating response and to examine: 1) the independence of the prebronchodilator forced expiratory volume in one second (FEV1); and 2) the reproducibility of the bronchodilating response. Bronchodilating responses (increases in FEV1 60 min after salbutamol 400 micrograms and ipratropium bromide 80 micrograms) on six test occasions, during two years, of 183 patients (72 asthma, 111 chronic obstructive pulmonary disease (COPD)) from a large bronchodilator intervention study were used. The dependence of the prebronchodilator FEV1 was investigated both between patients (cross-sectional analysis) and within patients (longitudinal analysis) by means of linear regression analysis. The reproducibility of the bronchodilating response was calculated by means of the coefficients of variation (CVs) of the six bronchodilating responses during two years. The CVs of the six expression indices were compared by analysis of variance (ANOVA). No index was independent of the prebronchodilator FEV1. However, some indices were significantly more dependent on the prebronchodilator lung function and, therefore, less reproducible than others. The "% initial" index (change as a percentage of the prebronchodilator value) was the most dependent on the prebronchodilator lung function and had the worst reproducibility (CV ranged from 50-61%). The "% possible" (change as a percentage of the predicted minus prebronchodilator value) and "% achievable" (change as a percentage of the maximal postbronchodilator minus prebronchodilator value) indices were the least dependent on the prebronchodilator value and had the highest reproducibility (CV ranging from 34-53%).(ABSTRACT TRUNCATED AT 250 WORDS)
Lung function in relation to silicosis and silica exposure in granite workers
Authors: Ng TP , Chan SL
Published: November 2022

Lung function tests (forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC %) were related to silica exposure and the extent of radiological opacities in a study of 206 active and 132 previously employed granite workers from two quarries. The investigations included detailed personal interviews, spirometric testing and radiographic examination of the chest. The chest X-ray films were read randomly and independently by three readers, using International Labour Office (ILO) standard films. Cumulative exposure to respirable silica (mg.m-3-yr) and total granite dust (million particles per cubic foot (mppcf-yr)) were estimated for each subject based on his years of employment at various jobs and historical and current measurements of quarry-, period- and job-specific exposures. The results suggest that chronic simple silicosis, especially for profusion category 2 and 3, was associated with significant lung function loss. As expected, mixed dust fibrosis was associated with little or no functional disturbance. Massive fibrosis was associated with significant obstructive and restrictive impairment. No additional effect of exposure to respirable silica on lung function loss was found after allowing for the presence of "silicosis". However, exposure to total dust (mppcf-yr) appeared to be associated with some lung function loss independent of silicosis. Our results indicate that chronic simple silicosis is not a benign disease; silica exposure is the primary cause, but the lung function loss in silicotics is directly attributable to the fibrotic lung disease. However, exposure to total granite dust beyond the respirable size range may separately produce additional lung function loss.
Toxoplasma pneumonitis: fatal presentation of disseminated toxoplasmosis in a patient with AIDS
Authors: Bergin C , Murphy M , Lyons D , Gaffney E , Mulcahy FM
Published: November 2022

Toxoplasma gondii infection is an uncommon cause of pneumonitis in patients with acquired immune deficiency syndrome (AIDS). We report a case of fatal pulmonary toxoplasmosis, which clinically resembled Pneumocystis carinii pneumonia (PCP). Conventional diagnostic methods for toxoplasmosis lack sensitivity. Bronchoscopy and histological evaluation of transbronchial biopsy specimens failed to identify the infecting organism. At autopsy there was evidence of disseminated infection.
Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study
Authors: Annesi I , Oryszczyn MP , Neukirch F , Orvoen-Frija E , Korobaeff M , Kauffmann F
Published: November 2022

Associations of upper airways disorders (UAD) with forced expiratory volume in one second (FEV1) and bronchial methacholine response were studied, taking smoking habits into account. We used epidemiological data drawn from a population of 324 men, aged 27-58 yrs. Lower FEV1 level was related to hay fever (p = 0.01), usual (p = 0.01) and chronic (p = 0.02) rhinitis and common cold on the day of examination (p = 0.04). Allowance for the major potential confounding factor, tobacco smoking, showed similar results. Bronchial methacholine response was heightened in men reporting hay fever compared to those without (p = 0.01) but also in men reporting chronic rhinitis (p = 0.06), a group which did not exhibit skin prick test positivity more often than other subjects. Exclusion of asthmatics and taking into account smoking and skin prick test positivity yielded mostly similar results. Our data support the hypothesis of an association between lung impairment, as assessed by lower FEV1 and bronchial hyperresponsiveness to methacholine, and different types of UAD, allergic or not.
New drugs for asthma
Authors: Barnes PJ
Published: November 2022

Several new drugs are now under development for the treatment of asthma, either as improvements to existing classes of therapy or as novel agents. Amongst bronchodilators, long-acting inhaled beta 2-agonists (salmeterol and formoterol) look very promising and there is also interest in selective phosphodiesterase inhibitors, K+ channel-openers and nitrodilators. There are several new inhaled corticosteroids under development and more selective agents include leukotriene antagonists, 5-lipoxygenase inhibitors, bradykinin and tachykinin antagonists and immunomodulators. In the future, adhesion molecule inhibitors and cytokine inhibitors may be developed.
Massive pleural effusion: an unusual presentation of Castleman's disease
Authors: Reynolds SP , Gibbs AR , Weeks R , Adams H , Davies BH
Published: November 2022

Giant lymph node hyperplasia (Castleman's Disease) is a rare cause of pleural effusion. We report the case of a 51 yr old West Indian male, who presented with a recurrent massive pleural effusion, due to a tumour arising from the pleura. He underwent parietal pleurectomy and subtotal excision of the tumour. Histological analysis of the specimen showed the features of multicentric Castleman's disease. Nine months following surgery he remains well, with no recurrence of the effusion.
Chronic extrinsic allergic alveolitis in a family with idiopathic pulmonary fibrosis: the importance of histological diagnosis
Authors: van Valenberg PL , Lammers JW , van den Hout HA , Molema J , van Herwaarden CL
Published: November 2022

We report a patient who presented with progressive exertional dyspnoea, chronic cough and radiographic signs of interstitial lung disease. Since several of his family members were known to have familial idiopathic pulmonary fibrosis he was also suspected to suffer from this disease. After thorough investigation, including histological examination of lung biopsies obtained by thoracoscopy, a diagnosis of chronic extrinsic allergic alveolitis was made. Current knowledge of familial idiopathic pulmonary fibrosis is discussed. This case report underlines the importance of a histological diagnosis in interstitial lung disease.
Outcome of respiratory distress syndrome at 28 days: a prospective longitudinal study
Authors: Van Lierde S , Smith J , Devlieger H , Eggermont E
Published: November 2022

Fifty eight newborn infants with respiratory distress syndrome (RDS) were prospectively studied, in order to determine clinical variables prognostic of poor outcome at 28 days. Twenty six infants survived without bronchopulmonary dysplasia (BPD), 13 had Type 1 BPD, 4 had Type 2 BPD and 15 infants died before 28 days. Survivors without BPD had higher birthweights and gestational ages. Among the other infants, severity of initial lung disease was the best discriminator between outcome groups: Type 1 BPD infants had the best lungs at onset, and the nonsurvivors had the worst lungs. Stepwise multiple logistic regression identified gestational age and the ventilatory index number 1 (VI1) (= respirator frequency x maximal inspiratory pressure) at day 3 as the most useful variables to predict "poor outcome" (nonsurvival or Type 2 BPD). Ninety five percent of the infants were correctly classified using a cut-off probability of 0.5. We conclude that RDS outcome at 28 days is determined at a very early stage and that poor outcome can be predicted with reasonable accuracy at three days of age.
Lung allograft transplantation: indications, preoperative assessment and postoperative management
Authors: Heritier F , Madden B , Hodson ME , Yacoub M
Published: November 2022

In spite of a shortage of available donors, an increasing number of heart-lung transplantations have been performed within the last decade. This procedure, first limited to patients with pulmonary vascular disease, has been successfully extended to patients with end stage lung disease, including cystic fibrosis. More recently, single lung, double-lung and bilateral single lung transplantation have become other therapeutic options. Better selection of patients and donors as well as improvements in surgical techniques and immunosuppression regimens have contributed to the reduction in the high perioperative mortality experienced in the early stages. Moreover, the introduction of daily spirometry and transbronchial lung biopsies have permitted early and reliable diagnosis of opportunistic infection and rejection. The most serious late complication of lung transplantation is obliterative bronchiolitis and further research is urgently required to improve diagnosis and management of this condition.
Incidence of community-acquired pneumonia and Chlamydia pneumoniae infection: a prospective multicentre study
Authors: Almirall J , Morato I , Riera F , Verdaguer A , Priu R , Coll P , Vidal J , Murgui L , Valls F , Catalan F , et al.
Published: November 2022

This one year prospective multicentre study was designed to determine the incidence of community-acquired pneumonia in adults. It was carried out in primary health care centres and three reference hospitals, located in the 'Maresme' region (Barcelona, Spain) serving a population of 39,733 subjects over 13 years of age. Patients suspected of having contracted community-acquired pneumonia were visited by their family doctors and referred to the three reference hospitals for confirmation of the diagnosis. Patients attending the emergency services of these hospitals were also included. Urine and blood samples were obtained for culture, antigen detection, blood count, serological tests, blood gases and biochemical profile. The diagnosis of community-acquired pneumonia was made in 105 patients. Forty-six patients had an identifiable microbial etiology. Chlamydia pneumoniae was the most common pathogen (16 cases) followed by Streptococcus pneumoniae (13 cases) and Mycoplasma pneumoniae (8 cases). In conclusion; the annual incidence rate of community-acquired pneumonia in adults in this area was 2.6 cases per 1,000 inhabitants and Chlamydia pneumoniae was the most frequent causative pathogen.
The effect of oral midazolam and diazepam on respiration in normal subjects
Authors: Mak KH , Wang YT , Cheong TH , Poh SC
Published: November 2022

Benzodiazepine have been shown to suppress ventilatory responses to hyperoxic hypercapnia (HCVR) and isocapnic HVR when taken parenterally. Most patients would, however, prefer to take an oral rather than parenteral preparation but the effect of oral benzodiazepine on these ventilatory responses has not been well studied. We therefore studied the effect of oral midazolam (7.5 mg) and diazepam (5 mg) both given orally on resting ventilation and respiratory drive, as assessed by HCVR and HVR. Flumazenil, a specific benzodiazepine antagonist, was administered intravenously to reverse the effect. A mental alertness-drowsiness index in five grades, from 1 (awake and alert) to 5 (asleep), was used to assess the sedation effect. Six normal male subjects, (aged 31 +/- 1.6 yrs) (mean +/- SD), participated in the study. Mean resting ventilation, and ventilatory response to HCVR and HVR were not significantly altered by these drugs when taken orally. Flumazenil also had not significant effect on HCVR and HVR. However the mental alertness-drowsiness index rose from 1 to 2.83 with oral midazolam and reversed to 1.25 with flumazenil. Similarly, this index increased from 1 to 2.25 after oral diazepam and reversed to 1.42 after flumazenil. In conclusion, we found that even though oral midazolam and diazepam produced a significant sedation effect, which was reversed with flumazenil, the drugs had no effect on ventilation at rest and the ventilatory responses to hypoxia and hypercapnia.
Effect of positive expiratory pressure on breathing pattern in healthy subjects
Authors: van der Schans CP , de Jong W , de Vries G , Postma DS , Koeter GH , van der Mark TW
Published: November 2022

The purpose of this study was to register breathing patterns, in healthy subjects, during breathing with a positive expiratory pressure. Integrated electromyographic (IEMG) activity of the following muscles was assessed: scalene muscle, parasternal muscle and abdominal muscles, using surface electrodes. Inspiration time, expiration time, total breathing cycle time, tidal volume and breathing frequency were measured using a water-sealed spirometer. Functional residual capacity was measured using a body plethysmograph. Oxygen uptake and carbon dioxide output were measured using an automatized ergometry set-up. All measurements were performed during undisturbed breathing and during breathing with positive expiratory pressures of 5 and 15 cmH2O. Phasic activity, but not tonic activity, of the scalene muscles and the abdominal muscles increased significantly during breathing with the expiratory pressures. No significant change was observed in phasic or tonic activity of the parasternal muscle. Mean (SD) tidal volume increased significantly from 0.8(0.2) l during undisturbed breathing to 1.1(0.3) l and 1.5(0.7) l during breathing with the expiratory pressures of 5 cmH2O and of 15 cmH2O, respectively. Respiration times, breathing frequency, oxygen uptake, carbon dioxide output and functional residual capacity remained unchanged. It can be concluded that, in healthy subjects, positive expiratory pressure increases tidal volume by activity of both expiratory and inspiratory muscles, while functional residual capacity remains unchanged. The changes appeared to be pressure dependent.
Rheology of mucus and transepithelial potential difference: small airways versus trachea
Authors: App EM , Zayas JG , King M
Published: November 2022

The transfer of water across the airway epithelium is closely related to the transepithelial potential difference (PD). Thus, PD should be directly involved in the regulation of airway intraluminal water content and, by extension, mucus rheology. Experiments by Boucher and co-workers (J Appl Physiol, 1980; 48: 169; and 1981; 51: 706) indicated that the values of PD in the small airways of dogs were considerably lower than in the trachea or mainstem bronchus. This fact suggests that water is increasingly removed from the airway lumen in the cephalad direction, and provides a possible mechanism whereby airway flooding is avoided as the total airway cross-section diminishes mouthward. We investigated this possibility by collecting and analysing mucus from the small airways and trachea of anaesthetized dogs and comparing our findings with measurements of PD. Mucus was collected on a cytology brush placed against the wall of the airway. Tracheal samples were taken from the lower lateral or anterior trachea, while small airway samples were taken from a 6th or 7th generation bronchus, chosen at random from either side. Measurements of PD were made at comparable sites. The mucus was analysed for its viscoelastic properties using the magnetic microrheometer technique. PD in the 6th-7th generation bronchus was significantly less than in the lower trachea (4.1 +/- 1.3 vs 17.2 +/- 7.1 mV). The rigidity of mucus collected from the small airways (log mechanical impedance (G*) at 100 rad.s-1) was significantly less than in the trachea (2.81 +/- 0.22 vs 3.01 +/- 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)
Thymomodulin increases HLA-DR expression by macrophages but not T-lymphocyte proliferation in autologous mixed leucocyte reaction
Authors: Balbi B , Valle MT , Oddera S , Manca F , Rossi GA , Allegra L
Published: November 2022

Thymomodulin (TMD), a thymic biological response modifier, stimulates the release of tumour necrosis factor (TNF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in macrophage-lymphocyte cultures. We investigated the effects of the cytokines released in cultures with TMD, on the expression of human leucocyte antigen-DR (HLA-DR) antigens by alveolar macrophages (AM) and the T-cell proliferation induced in autologous mixed leucocyte reaction (AMLR) cultures or by T-cell mitogens. Among freshly isolated AM, 84 +/- 4% were HLA-DR positive, and this proportion was significantly reduced after 24 h cultures (60 +/- 3%, p < 0.05). In cultures without peripheral blood (PBL) lymphocytes, TMD did not change HLA-DR expression by AM CHLA-DR+AM); whilst in the presence of autologous PBL lymphocytes, TMD induced an increase in the proportions of HLA-DR+AM (TMD 100 micrograms.ml-1 79 + 3%, p < 0.04 vs control cultures). However, TMD did not change the ability of AM to induce T-cell proliferation in AMLR between AM and PBL lymphocytes. In contrast, in PBL mononuclear cell cultures, TMD induced a further increase of the cell proliferation due to the T-cell mitogens interleukin-2 (IL-2) or phytohaemagglutinin (PHA) (p < 0.05 vs each control culture with mitogens) or anti-CD3 antibodies (p < 0.03 vs control cultures). Thus, the cytokines released in cultures with TMD enhance macrophage HLA-DR expression. Whilst this phenomenon is not associated with changes in the ability of AM to stimulate T-cell proliferation, TMD is able to increase the mitogen-induced T-cell proliferation.
Primary malignant non-Hodgkin's lymphoma of the lung arising in mucosa-associated lymphoid tissue (MALT)
Authors: Roggeri A , Agostini L , Vezzani G , Sabattini E , Serra L
Published: November 2022

We describe a 10 yr follow-up of a patient with a primary malignant non-Hodgkin's lymphoma of the lung, arising in mucosa-associated lymphoid tissue (MALT). Although the patient was not treated with chemotherapy or radiotherapy, no peripheral spread occurred, confirming that MALT-associated lymphomas apparently remain localized until late in the course of the disease.
Effects of intravenous broxaterol on respiratory drive and neuromuscular coupling in COPD patients
Authors: Gigliotti F , Gurrieri G , Duranti R , Gorini M , Scano G
Published: November 2022

Broxaterol, a new selective beta 2-agonist, has been shown to exert inotropic effects on both fresh and fatigued canine diaphragm. We evaluated the effect of broxaterol on the activation and force output of the respiratory muscles in patients with chronic obstructive pulmonary disease (COPD). We studied 9 patients with moderate to severe COPD. Each patient was infused with saline and Broxaterol (200 micrograms) in saline alternately. We measured lung volumes, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), breathing pattern, P0.1, respiratory muscle EMG (diaphragm, EMGd, and parasternal, EMGp) and P0.1/EMGd ratio. Measurements were made under control conditions and at 15, 30, 60, and 120 min after each infusion. Broxaterol, but not saline, resulted in a slight but significant increase in vital capacity (VC), forced expiratory volume in one second (FEV1) and MIP, and a decrease in functional residual capacity (FRC). Breathing pattern did not change, while EMG significantly decreased, and P0.1/EMGd significantly increased in 5 of the 9 patients after broxaterol. These data seem to indicate that by partially unloading the respiratory muscles, broxaterol results in decreased muscle activation (EMG). Increase in chest wall neuromuscular coupling (P0.1/EMGd) may also be observed.
Minor acute effect of an inhaled corticosteroid (budesonide) on bronchial hyperresponsiveness to methacholine in children with asthma
Authors: van Essen-Zandvliet EE , Hop WC , de Jong H , Ferwerda A , Kerrebijn KF
Published: November 2022

Several studies have shown that long-term administration of inhaled corticosteroid reduces airway hyperresponsiveness. This study was performed in order to exclude an acute effect of inhaled corticosteroid. In a double-blind, randomized, cross-over study, children with asthma, who had never used inhaled or oral corticosteroid, received a single dose of 0.8 mg budesonide or placebo on two separate days, with an interval of at least 48 h. On each test day, baseline forced expiratory volume in one second (FEV1) and methacholine responsiveness (expressed as provocative dose producing a 20% fall in FEV1 (PD20) to methacholine, in doubling dose) were measured. Both measurements were repeated 2 and 5 h after administration of the drug. Twenty children were included in the study. FEV1 showed a mean increase of 1% at 5 h on the budesonide day, and a decrease of 2% on the placebo day (p = 0.01). PD20 increased by 0.1 doubling dose on the budesonide day, and decreased by 0.4 doubling dose on the placebo day. These changes are within the measurement variation (p = 0.06). We conclude that a single dose of 0.8 mg budesonide has a minor effect on methacholine responsiveness 5 h after administration in children with asthma. It is unlikely that such an effect interferes with the interpretation of data collected in long-term studies.