bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhaled formoterol during one year in asthma: a comparison with salbutamol
Authors: Arvidsson P , Larsson S , Lofdahl CG , Melander B , Svedmyr N , Wahlander L
Published: November 2022

Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.
Cardiovascular autonomic nerve function in patients with hypoxaemic chronic obstructive pulmonary disease
Authors: Stewart AG , Waterhouse JC , Howard P
Published: November 2022

Intraneural hypoxaemia is recognized as a pathogenic mechanism in diabetic neuropathy. A similar pathophysiological process may occur in chronic obstructive pulmonary disease (COPD). Autonomic neuropathy is not recognized in COPD. We compared 96 patients with hypoxaemic COPD to 22 age-matched control subjects to see whether autonomic dysfunction occurs in COPD and whether there was any correlation with the severity of hypoxaemia. The cardiovascular autonomic tests consisted of heart rate responses (mainly parasympathetic function) to a Valsalva manoeuvre, deep breathing and postural change and blood pressure responses (mainly of sympathetic origin) to postural change and sustained handgrip. Early autonomic neuropathy is defined as one abnormal test and definite autonomic neuropathy as two abnormal tests according to the normal range. These autonomic tests were reproducible in our study population. Although the symptoms and signs of autonomic neuropathy were rare, definite autonomic dysfunction was found in 35%, and early autonomic neuropathy in a further 47%, of patients whose arterial oxygen tension (PaO2) was less than 8 kPa (60 mmHg). Only 18% of the control group had evidence of an age-related early autonomic dysfunction. Parasympathetic autonomic dysfunction was significantly correlated with PaO2 whilst the sympathetic tests were relatively normal. Correction of hypoxaemia for one hour or administration of ipratropium bromide or terbutaline had no effect on autonomic function. Subclinical autonomic neuropathy is a feature of hypoxaemic COPD. Its importance in the disease process and its role in prognosis needs evaluation.
The significance of a residual mediastinal mass following treatment for aggressive non-Hodgkin's lymphomas
Authors: Tredaniel J , Brice P , Lepage E , Bris C , Marolleau JP , Ferme C , Hennequin C , Fermand JP , Frija J , Gisselbrecht C , et al.
Published: November 2022

The chest radiographs of 252 patients with aggressive non-Hodgkin's lymphoma, prospectively treated according to one of three protocols of combination chemotherapy, were reviewed to determine the incidence and prognostic significance of mediastinal abnormalities following treatment. Residual mediastinal masses were defined as any abnormality, greater than 2 cm in diameter, that had initially responded to chemotherapy and then remained stable in size for at least three months after its maximal response, together with the disappearance of all other clinical and biological signs of active lymphoma. At the end of treatment, 21 (8%) patients had some residual mediastinal abnormality. The predominant histological pattern was the diffuse large cell subtype (p less than 0.001). Disease free survival and overall survival for these patients were similar to those observed among patients in complete remission without a persisting radiological mass after treatment. We conclude that mediastinal residual masses after completion of treatment for aggressive lymphoma are frequent and do not indicate a poorer prognosis. Such patients can be observed clinically without any need for additional chemotherapy or radiotherapy.
T-cell dominated inflammatory reactions in the bronchi of asthmatics are not reflected in matched bronchoalveolar lavage specimens
Authors: Poulter LW , Norris A , Power C , Condez A , Schmekel B , Burke C
Published: November 2022

Samples of bronchoalveolar lavage (BAL) and endobronchial biopsies were obtained from five patients with clinically diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. Significantly raised numbers of T lymphocytes, CD45RO+ lymphocytes, RFD1+ macrophage-like cells and RFD7+ macrophages were seen in the bronchial biopsies. In contrast four out of five of the BAL specimens showed a normal differential cell count, the one exception being a patient exhibiting a degree of lymphocytosis. Further, immunocytological investigation demonstrated a normal distribution of T-cell subsets and macrophage subsets in asthmatic BAL with the exception that in four out of five of these patients a raised number of macrophage-like cells exhibiting phenotypic markers of monocytes was observed. Correlation between BAL and biopsy data was seen in the number of CD45RO+ T-cells present. No other parameters exhibited a significant correlation. Raised expression of HLA-DR was recorded in all asthmatic biopsies, yet lavage cells from the same patients failed to exhibit any increase of HLA-DR density over normal. It is concluded that the immune-associated inflammation present in endobronchial biopsies of clinically stable asthmatics is not reflected in bronchoalveolar lavage samples taken from the same patients.
Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients
Authors: Pujet JC , Dubreuil C , Fleury B , Provendier O , Abella ML
Published: November 2022

The aim of this study was to compare the pulmonary effects of a single dose of celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400 mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a double-blind randomized cross-over study in 10 stable asthmatic patients (mean age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5 +/- 0.7 l. A three-day washout period preceded each treatment period. Measurements of respiratory function were done before treatment and after 90, 120 and 180 min. There was a significant increase of FEV1 (+12%) and forced vital capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (-9%) after propranolol. Concerning the combination, celiprolol inhibits the bronchoconstrictor effects of propranolol. We conclude that celiprolol has bronchosparing properties in asthmatic patients, and even improves some of the ventilatory parameters.
Decrease in haematocrit with continuous positive airway pressure treatment in obstructive sleep apnoea patients
Authors: Krieger J , Sforza E , Delanoe C , Petiau C
Published: November 2022

Previous preliminary results have shown an overnight decrease in haematocrit and red cell count after the first night of treatment with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) patients. The present study was designed to confirm these preliminary data, and to analyse the long-term effects of CPAP. The haematocrit and red cell count (RCC) were measured in 80 OSA patients on two consecutive mornings, after an untreated night and after a CPAP treatment night. The haematocrit and RCC significantly decreased with CPAP (from 44.0 +/- 0.5 to 42.4 +/- 0.4%, p less than 0.0001 and from 4.769 +/- 0.051 to 4.597 +/- 0.052 x 10(12) red cells.l-1, p less than 0.0001, respectively). Neither the decrease in haematocrit nor the decrease in RCC were correlated with the decrease in urine volume or flow which occurred with CPAP. Thirty five of these patients remained untreated for 45 +/- 4 days, before home treatment with CPAP was initiated. The haematocrit and RCC had returned to values close to those before initial treatment and decreased again after the first treatment night. Twenty one of the patients were re-evaluated after at least one year of home treatment with CPAP, again on two consecutive nights either with CPAP or untreated. The follow-up, post-CPAP haematocrit and RCC were slightly and nonsignificantly higher than after the baseline CPAP night, but still lower than after the baseline untreated night (p less than 0.02). After the untreated follow-up night, no significant change in haematocrit was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonadrenergic, noncholinergic airway inhibitory nerves
Authors: Lammers JW , Barnes PJ , Chung KF
Published: November 2022

Nonadrenergic, noncholinergic (NANC) nerves, which cause relaxation of airway smooth muscle, have been described in several species including man. Stimulation of efferent vagus nerves during cholinergic and adrenergic blockade induces a pronounced bronchodilation in the cat. In more recent studies in man, capsaicin inhalation or mechanical irritation of the larynx, under conditions of cholinergic and adrenergic blockade, have been shown to cause a transient bronchodilator response. There is some evidence that neuropeptides such as vasointestinal peptide (VIP) or peptide histidine methionine (PHM) may be the neurotransmitter of NANC nerves, but this is not conclusive. Nitric oxide may be another neurotransmitter. In mild asthma, the NANC bronchodilator response is similar to that observed in normal subjects; on the other hand, a reduction in VIP immunoreactivity has been reported in more severe patients. The contribution of NANC dilator nerves in pathophysiological situations is not known, but their effect may be modulated during allergic responses. Use of antagonists or inhibitors of putative neurotransmitters, and molecular biological techniques will be useful in defining both the physiological and pathophysiological roles of NANC inhibitory nerves in the airways.
Functions of proteins and lipids in airway secretions
Authors: Jacquot J , Hayem A , Galabert C
Published: November 2022

Proteins and lipids synthesized by airway secretory cells or transudated are active components in the protection of respiratory epithelium. Proteins and ions are involved in the control of mucus hydration. Secretory proteins, such as secretory immunoglobulin A (IgA), transferrin and lysozyme, participate in the airway antibacterial defence. Other biochemical components found in secretions, such as anti-inflammatory and antioxidant agents as well as antiproteases, contribute significantly to the protection of the underlying epithelium.
Blastomycosis in Africa: a new case from Tunisia
Authors: Jerray M , Hayouni A , Benzarti M , Klabi N , Garrouche A
Published: November 2022

Although blastomycosis is prevalent in the North American continent, it occurs only sporadically in Africa. We describe a 42 yr old patient who complained of intermittent cough and haemoptysis. Clinical findings were strongly suggestive of lung cancer. The diagnosis of pulmonary blastomycosis was made at thoracotomy. This rather unusual disease in our areas caused a considerable delay in securing the diagnosis and we suggest that this infection may be found elsewhere in Africa and the distribution may be wider than has previously been suspected.
A bronchoscopic brush biopsy study of large airway mucosal pathology in smokers with chronic bronchitis and in healthy nonsmokers
Authors: Riise GC , Larsson S , Andersson BA
Published: November 2022

We investigated the use of bronchial brush biopsies of the bronchial epithelium as a diagnostic tool in common airway diseases. Flexible fibreoptic bronchoscopy was performed on 22 smokers with nonobstructive chronic bronchitis and on 14 healthy nonsmoking individuals. Ten of the smokers had recurrent infectious exacerbations. Cell samples were taken from carinal and subsegmental levels of the bronchial tree with a standard cytological brush, and a differential count was made of the different cell types. Smokers with chronic bronchitis had significantly more goblet cells (mean 20.0, SD 8.6), and less ciliated epithelial cells (mean 74.1, SD 9.4), than the healthy nonsmokers (mean 9.2, SD 3.9 and mean 84.7, SD 6.6, respectively). No such changes were found between the chronic bronchitis groups with or without infectious exacerbations. Thus, bronchial brush biopsies can be used as a complement to standard bronchial biopsies in the investigation of airway diseases other than pulmonary malignancies.
Serial assessment of pulmonary microvascular permeability in a patient developing the adult respiratory distress syndrome
Authors: Braude S , Baudouin S , Evans TW
Published: November 2022

Serial measurements of lung extravascular accumulation of 113mIndium-transferrin were made in a patient with acute respiratory failure during the development of the adult respiratory distress syndrome (ARDS). Abnormality of this index of pulmonary microvascular permeability antedated radiological change and appeared to predict the onset of frank ARDS.
Neuropathy in chronic obstructive pulmonary disease: a multicentre electrophysiological and clinical study
Authors: Jarratt JA , Morgan CN , Twomey JA , Abraham R , Sheaff PC , Pilling JB , Payan J , Mitchell JD , Tang O , Arnaud F , et al.
Published: November 2022

The incidence and type of neuropathy in patients with chronic obstructive pulmonary disease (COPD) were assessed. In a selected group of 89 patients, abnormal nerve conduction studies were found in 44%. Electrophysiological signs of a generalized peripheral neuropathy were found in 5-18%, depending on diagnostic criteria. Lesions which were thought to be due to compression or other forms of trauma were present in a further 24%. In the patients with peripheral neuropathy, the changes were distally predominant, affected mainly sensory fibres, and were consistent with an axonal type of neuropathy. There was a significant correlation between age and the incidence of peripheral neuropathy. Electrophysiological evidence of neuropathy was three times as common as clinical evidence. Much of the variation in the reported incidence of neuropathy in COPD is probably due to imprecise diagnostic criteria.
Branhamella catarrhalis respiratory infections
Authors: Barreiro B , Esteban L , Prats E , Verdaguer E , Dorca J , Manresa F
Published: November 2022

Branhamella catarrhalis is an aerobic Gram-negative diplococcus. It has been traditionally regarded as an oropharyngeal commensal and until recently was only identified as a pathogen in cases of bronchopulmonary infections. The aim of this study was to analyse the characteristics of the respiratory infections caused by B. catarrhalis and to know the antibiotic susceptibility of this microorganism. We retrospectively studied 32 lower respiratory tract infections, caused by B. catarrhalis (20 cases of bronchial infection and 12 cases of pneumonia), diagnosed between 1988-1989 in our hospital. All patients had an underlying disease; chronic obstructive pulmonary disease (COPD) and chronic heart disease being the most frequent. The aetiological diagnostic procedures were: sputum culture in 28 cases (15 in pure culture and 13 mixed), protected specimen brush (PSB) in three cases and transthoracic needle aspiration (TNA) in one case. Twenty B. catarrhalis isolates were penicillin and ampicillin-resistant, 11 in the pneumonia group and 9 in the bronchial infection group. All isolates were sensitive to amoxycillin-clavulanic acid and second generation cephalosporin. In our group four patients died. We conclude that B. catarrhalis is a not infrequent cause of respiratory infection, particularly in COPD patients, and that the high incidence of antibiotic resistance to penicillin and ampicillin should be taken into account before considering an empirical antibiotic treatment.
Parenteral administration of trypsin triggers lung emphysema
Authors: Reichart E , Boerkmann P , Plenat F
Published: November 2022

Eight weeks after a single intravenous injection of trypsin, more than half of 26 treated rats showed pulmonary emphysema, as demonstrated by a significant increase of the mean linear intercept (MLI = 107 microns) in comparison with 11 controls (69 +/- 15 microns) (mean +/- SD). As observed 56 days after the injection, the intraperitoneal administration of trypsin (24 rats) also leads to lung emphysema (MLI = 101-106 microns), as does endotracheal instillation of elastase (13 rats), (MLI = 108 microns). The intraperitoneal administration of trypsin in animals constitutes a model close to human pathology with which lung alterations in acute pancreatitis may be studied. Having no elastolytic properties, trypsin cannot directly induce emphysema. The observation of a pulmonary leucostasis in eight rats sacrificed early after the trypsin injection suggested that leucocyte trapping and activation are important for the genesis of this trypsin-triggered emphysema.
Ultrastructural and immunohistochemical studies on the ontogenic development of bronchus-associated lymphoid tissue (BALT) in the rat: special reference to follicular dendritic cells
Authors: Matsuura Y , Matsuoka T , Fuse Y
Published: November 2022

The ontogenic development of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the rat was studied ultrastructurally and immunohistochemically. In the late foetal period, only the alveolar macrophages showed a weak positivity for leucocyte common antigen, but no immune region associated (Ia) antigen was detected by monoclonal antibody, MAS 043. Mast cells were present. At 6 days of age, Ia-positive cells were observed in the alveolar wall and peribronchial interstitial tissue, and ultrastructurally there was an aggregation of the fibroblastoid mesenchymal cells. By 10 days of age, the aggregation of lymphoid cells together with S-100-positive reticulum cells had formed a BALT-like periarterial lymphoid sheath. In the adult animals, an obvious B-cell area was present in the central part and subepithelium of BALT, whilst in this area, S-100-positive, strongly Ia-positive cells with a dendritic form were observed. These dendritic cells appeared to be identical to the follicular dendritic cells (FDC) seen in the secondary follicles of lymphoid organs. Those cells may be derived from the fibroblastic reticulum cells, and may function to present antigen to lymphocytes.
Adaptation of cough reflex with different types of stimulation
Authors: Morice AH , Higgins KS , Yeo WW
Published: November 2022

Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory mechanics studied by multiple linear regression in unsedated ventilated patients
Authors: Peslin R , da Silva JF , Chabot F , Duvivier C
Published: November 2022

Respiratory mechanics during artificial ventilation are commonly studied with methods which require a specific respiratory pattern. An alternative is to analyse the relationship between tracheal pressure (P) and flow (V') by multiple linear regression (MLR) using a suitable model. The value of this approach was evaluated in 12 unsedated patients, mechanically-ventilated for acute respiratory failure, and most with a history of chronic obstructive or restrictive respiratory disease. After correction for the non-linear resistance of the endotracheal tube, the data were analysed with the linear first order model: P = P0 + E.V + R.V' where E and R are total respiratory elastance and resistance, and P0 is the static recoil pressure at end-expiration. After exclusion of the cycles which clearly exhibited muscular activity, a good fit was observed in 25 out of 36 records (relative root-mean-square error less than 10%); the values of E and R were reproducible within cycles, and consistent with the patient's condition and the ventilatory mode. The intrinsic positive end-expiratory pressure (PEEPi), as derived from P0 and the applied PEEP, averaged 1.1 +/- 1.0 hPa. Using more sophisticated models, allowing for mechanical non-homogeneity or non-linearity of R or E, rarely improved the fit and often provided unrealistic data. In several subjects the discrepancy between the data and the first order model was consistent with expiratory flow limitation, which may severely impair the analysis. We conclude that, except in the case of expiratory flow limitation, the method is useful for routine clinical use and better implemented with the simple linear model.
Influence of short-term passive smoking on symptoms, lung mechanics and airway responsiveness in asthmatic subjects and healthy controls
Authors: Jorres R , Magnussen H
Published: November 2022

We studied the acute effect of passive smoking on symptoms, lung mechanics and airway responsiveness. Twenty four patients with mild to moderate bronchial asthma (11 male and 13 female; mean(SD) age 34(15) yrs; forced expiratory volume in one second (FEV1) 91(17) % pred) were investigated. Sixteen of them had a history of passive smoke-induced respiratory symptoms. For comparison we studied 16 controls (7 male and 9 female; mean(SD) age 31(9) yrs; FEV1 106(13) % pred). On two different days, the subjects were exposed in an exposure chamber for one hour to either ambient air (Sham) or environmental tobacco smoke (ETS). During exposure to ETS, the mean concentrations of particles and CO were 3,095 micrograms.m-3 and 20.3 ppm, respectively. Before and immediately after exposure, symptoms and lung mechanics were assessed, followed by an inhalation challenge to determine the provocative concentrations of methacholine necessary to increase specific airway resistance (sRaw) by 100%, (PC100sRaw), and to decrease FEV1 by 20% (PC20FEV1). In the asthmatic subjects, during Sham exposure, mean (SEM) decrease of sRaw and FEV1 was 0.23(0.22) cmH2O.s and 0.04(0.03) l, respectively, (NS). During ETS, mean(SEM) decrease of sRaw and FEV1 was 0.55(0.46) cmH2O.s and 0.13(0.06) l, respectively. The significance of this decrease, however, disappeared when taking into account the individual variability of FEV1. Geometric mean(SEM) PC100sRaw and PC20FEV1 were 0.35(1.32) and 0.23(1.34) mg.ml-1 after Sham, and 0.34(1.37) and 0.28(1.36) mg.ml-1 after ETS, respectively, with no difference between the two study days. In the controls, the two exposure conditions did not exert any significant effects on sRaw, FEV1 and airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhaled beclomethasone improves the course of asthma and COPD
Authors: Dompeling E , van Schayck CP , Molema J , Folgering H , van Grunsven PM , van Weel C
Published: November 2022

The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction
Authors: Hawksworth RJ , O'Hickey SP , Lee TH
Published: November 2022

The purpose of this study was to determine the effect of pretreatment with indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction. In a double-blind, placebo-controlled, randomized trial nine asthmatic subjects underwent two hypertonic saline challenges, 60 min apart, on a control day and after premedication with indomethacin 50 mg or matching placebo, twice daily for three days. Premedication with indomethacin did not change airway responsiveness to the initial hypertonic saline challenge. The mean maximal % fall in specific airway conductance (sGaw) was 40.3, 44.1 and 47.6% on the control, placebo and indomethacin days, respectively. Subjects were significantly less responsive to the second hypertonic challenge as compared to the initial challenge on all three study days. There was a variable effect of indomethacin pretreatment on the refractory period. Five subjects lost their refractory period after indomethacin, when the variability of the test was taken into account. This suggests that there may be contributory mechanisms to the refractory period other than the release of protective prostanoid metabolites.
Steroid-induced myopathy and its significance to respiratory disease: a known disease rediscovered
Authors: Dekhuijzen PN , Decramer M
Published: November 2022

Skeletal muscle myopathy is a well-known side-effect of systemically administered corticosteroids. In recent years renewed attention is being paid to the involvement of the respiratory muscles and its consequent significance in pulmonary patients. Two different clinical patterns of steroid-induced muscular changes are known. In acute myopathy and atrophy after short term treatment with high doses of steroids, generalized muscle atrophy and rhabdomyolysis occur, including the respiratory muscles. Chronic steroid myopathy, occurring after prolonged treatment with moderate doses, is characterized by the gradual onset of proximal limb muscle weakness and may be accompanied by reduced respiratory muscle force. Animal studies demonstrated diaphragmatic myopathy and atrophy similar to the alterations in peripheral skeletal muscles. Fluorinated steroids induced selective type IIb (fast-twitch glycolytic) fibre atrophy, resulting in changes in contractile properties of the diaphragm. Non-fluorinated steroids may also induce histological, biochemical and functional alterations in the diaphragm. Observations in patients with collagen vascular disorders and with asthma and chronic obstructive pulmonary disease (COPD) underline the potential hazards of treatment with corticosteroids to respiratory muscle structure and function.
Consistency of sternal percussion performed manually and with mechanical thumper
Authors: Bohadana AB , Kraman SS
Published: November 2022

Auscultatory percussion is a technique that is potentially useful to study the acoustic behaviour of the chest. However, finger percussion, as used in this technique, has not been previously assessed for consistency. We calculated the intrasubject variability and short-term reproducibility of this technique in 10 healthy subjects. We examined several indices of the output sound of two series of sternal percussion manoeuvres performed one hour apart by the same examiner. The results were compared to those obtained during sternal percussion performed by a mechanical thumper. Consistency for both finger and thumper percussion varied from 4.8-20.6 (coefficients of variation) for various acoustic indices. For thumper percussion, the average results were not significantly different from those of finger percussion. We conclude that finger percussion of the sternum is sufficiently consistent to be used as a tool to investigate the acoustic behaviour of the chest.
Effects of repeated exposure to 4 ppm nitrogen dioxide on bronchoalveolar lymphocyte subsets and macrophages in healthy men
Authors: Sandstrom T , Helleday R , Bjermer L , Stjernberg N
Published: November 2022

Following the basal descriptive studies of the bronchoalveolar inflammatory cell response induced by single exposure with nitrogen dioxide (NO2) in man, it was considered important to clarify the cell response to repeated exposure with NO2. This investigation was, therefore, undertaken with bronchoalveolar lavage (BAL) 3 weeks before and 24 h after six repeated exposures with 4 ppm NO2 (7 mg.m-3) in ten healthy volunteers. The exposures were performed during 20 min and every second day. Analysis of the recovered BAL fluid demonstrated that repeated exposures to NO2 caused a lung cell response different from that reported after a single exposure. Amounts of lavaged alveolar macrophages, B-cells, and natural killer (NK)-cells were decreased and the T-helper-inducer/cytotoxic-suppressor cell ratio was altered, but there was no lymphocytosis or mastocytosis as after single exposure. Lymphocyte numbers in peripheral blood were reduced after exposure. These results suggest that repeated exposure with NO2 adversely affects the immune defence. This could contribute to the increased susceptibility to airway infections reported to be associated with NO2 exposure.
Pulmonary gas exchange response following allergen challenge in patients with allergic asthma
Authors: Lagerstrand L , Larsson K , Ihre E , Zetterstrom O , Hedenstierna G
Published: November 2022

Pulmonary gas exchange was studied in 8 patients with allergic asthma before and after allergen challenge. Ventilation-perfusion relationships were assessed by the multiple inert gas elimination technique and forced expiratory flow by conventional spirometry. Measurements were made before, 7-8 minutes, and 0.5, 2.5 and 5 hours after challenge. During baseline conditions all patients showed normal forced expiratory flow (FEV1 3.9 +/- 0.77 (SD) l) and gas exchange expressed as the dispersion of pulmonary blood flow, log SDQ (0.35 +/- 0.08), (one of the common descriptors of ventilation-perfusion (VA/Q) inequality). Immediately after challenge there were significant decreases in FEV1 (to 2.3 +/- 0.75 l) and arterial PO2 (from 13.1 +/- 0.9 to 9.5 +/- 1.2 kPa). The developed ventilation-perfusion inequalities were similar to those found in other asthma studies, i.e. mainly a broad (log SDQ increased to 0.73 +/- 0.30) and sometimes bimodal distribution of the perfusion. Thirty minutes after challenge FEV1 significantly improved to 3.2 +/- 1.18 l while log SDQ remained high (0.71 +/- 0.32). Two and a half hours after challenge log SDQ was reduced and almost normalized to 0.38 +/- 0.07. Five patients developed a late phase reaction with decreasing flow rates after 5 hours. Three of these patients also showed increased log SDQ. There was no clear relationship between gas exchange mismatch and reduced forced expiratory flow. The results support the hypothesis that reduced expiratory flow and gas exchange impairment are caused by different pathophysiological mechanisms.
Protective effect of loop diuretics, piretanide and frusemide, against sodium metabisulphite-induced bronchoconstriction in asthma
Authors: Yeo CT , O'Connor BJ , Chen-Worsdell M , Barnes PJ , Chung KF
Published: November 2022

We determined whether the loop diuretic, piretanide, had a similar inhibitory action against sodium metabisulphite (MBS)-induced bronchoconstriction in asthmatic subjects as frusemide and, if so, its duration of action. In the first study, we compared the effect of inhaled placebo, piretanide (24 mg), or frusemide (40 mg), on the provocative concentration of MBS needed to cause a 20% fall in baseline forced expiratory volume in one second (FEV1) (PC20MBS) in 12 mild asthmatic subjects before, immediately after, and at 1.5, 3, 6, and 24 h, after inhalation. Both piretanide and frusemide induced a significant diuresis lasting at least 24 h. Frusemide caused a mean 3.8 fold (95% confidence interval: 2.3-6.3 fold), piretanide a 2.5 fold (1.8-3.4 fold) and placebo a 1.7 fold (1.5-1.9 fold) increase in PC20MBS. The effects of frusemide and piretanide were significantly greater than that of placebo. At later time points, tachyphylaxis to the bronchoconstrictor effects of MBS was observed during the placebo limb. In the second study, we measured PC20MBS at 90 min after inhalation of either placebo, piretanide (24 mg), or frusemide (40 mg). No significant difference in PC20MBS was observed. We conclude that piretanide in addition to frusemide significantly inhibits MBS-induced bronchoconstriction and that this action is short-lived over less than 90 min. Frusemide was more potent in inhibiting MBS-induced bronchoconstriction despite causing a smaller diuretic effect than piretanide. The basic mechanism of action of the loop diuretics in the airways remains unclear.
Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group
Authors: Muir JF , Bertin L , Georges D
Published: November 2022

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.
Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow
Authors: Kelly WT , Baile EM , Brancatisano A , Pare PD , Engel LA
Published: November 2022

Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators from the airways, thus affecting the duration and severity of bronchospasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: 1) increased negative intrathoracic pressure swings (-25 +/- 1 cmH2O) induced by an inspiratory resistance; 2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and 3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition.
European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design
Authors: Pauwels RA , Lofdahl CG , Pride NB , Postma DS , Laitinen LA , Ohlsson SV
Published: November 2022

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.
Calibration of aerosol output from the Mefar dosimeter: implications for epidemiological studies
Authors: Dennis JH , Avery AJ , Walters EH , Hendrick DJ
Published: November 2022

Standardized methods for the measurement of airway responsiveness may use the Mefar MB3 inhalation dosimeter to generate standard doses of methacholine aerosol. The manufacturer provides calibrated output data for every nebulizer, so that a standard output may be achieved by varying nebulization time. This output is, however, measured by weight loss (WL), which may over-estimate true aerosol output (AO) because of concomitant evaporation. We have used a chemical (fluoride) tracer method to measure AO directly from two batches of Mefar nebulizers (batch 1 n = 5, batch 2 n = 10) and compared results with manufacturer's quoted WL. Mean AO from batch 1 was 10.56 mg.s-1 (range 9.50-11.63, SD = 0.92 mg.s-1), and mean AO from batch 2 was 5.66 mg.s-1 (range 4.92-6.58, SD = 0.57 mg.s-1), implying that AO varied little within, but substantially between, the two nebulizer batches. Manufacturer's quoted WL does not reflect this near two fold difference: mean WL batch 1 = 14.0 mg.s-1 (range 13-15 mg.s-1); mean WL batch 2 = 11.1 mg.s-1 (range 11-12 mg.s-1). The median aerosol fractions (AO/WL) for batches 1 and 2 were 76% (range 65-83%) and 50% (range 43-60%), respectively. Similar results were obtained with our own measurement of weight loss. This implies that if the median nebulizers of batches 1 and 2 were calibrated (as recommended) by the manufacture's WL to deliver a presumed 100 micrograms methacholine dose, the actual doses delivered would be 76 micrograms and 50 micrograms, the range for all 15 nebulizers being 43-83 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
Chlamydia pneumoniae infection in acute exacerbations of COPD
Authors: Blasi F , Legnani D , Lombardo VM , Negretto GG , Magliano E , Pozzoli R , Chiodo F , Fasoli A , Allegra L
Published: November 2022

Chlamydia pneumoniae, strain TWAR, is a frequent causative agent of acute respiratory disease. We assessed the incidence and prevalence of Chlamydia pneumoniae infections in COPD. We studied, from January 1990 to May 1991, 142 out-patients with acute purulent exacerbations of chronic obstructive pulmonary disease (COPD) and 114 healthy control subjects. Oropharyngeal swab specimens were collected at each exacerbation and analysed using a high definition monoclonal indirect fluorescent antibody test for Chlamydia pneumoniae identification. Immunoglobulins G and M (IgG and IgM) fractions of antibodies to Chlamydia pneumoniae were studied by microimmunofluorescence test. Prevalence of specific IgG was 63% in COPD, and 46% in controls (Chi-squared test p = 0.007). Moreover, mean titre of IgG was significantly higher in COPD than in controls. Five patients were positive for specific IgM (> or = = 1:16), and one had a fourfold increase of IgG titre; four of these patients had been treated with ciprofloxacin 1 g.day-1 for 10 days, and two with erythromycin, 3 g.day-1 for 14 days, with remission of signs and symptoms of exacerbation. Chlamydia pneumoniae identification was always negative. Our data suggest that Chlamydia pneumoniae infection is a rather frequent event in COPD, since at least 4% of exacerbations may be associated with it.
Restrictive treatment policy for pulmonary tuberculosis in a low prevalence country
Authors: Norregaard J , Grode G , Viskum K
Published: November 2022

In Denmark, treatment of tuberculosis is generally recommended only if the diagnosis is confirmed bacteriologically. This policy may cause a delay in treatment, if the patients are smear negative. We investigated the duration of the treatment delay, and whether the delay would cause any serious health problems for the individual, or risk of contact infections, in a retrospective examination of 324 cases of pulmonary tuberculosis. The mean treatment delay was longer in the oldest age group. Concerning death due to delay, we found no risk for those patients who were not weakened by other disease or old age. Only 11 patients (3.6%) over the age 10 yrs were treated without bacteriological confirmation (1% for Danes). The infection risk from the smear negative but culture positive patients was minimal, as only one subject was definitely infected from a smear negative patient. However, a risk of transmission exists from patients who are initially culture negative but later become smear positive. In conclusion, we find the epidemiological and individual risks sufficiently low to continue our rather restrictive treatment policy.
The clinical efficacy of inhaled nedocromil sodium (Tilade) in the treatment of asthma
Authors: Edwards AM , Stevens MT
Published: November 2022

Inhaled nedocromil sodium, an anti-inflammatory agent for the maintenance treatment of asthma, has been the subject of many clinical trials but only a proportion have been published. This paper provides an overview analysis of all known placebo-controlled, double-blind, randomized therapeutic trials. Both single centre and multicentre trials are included. A comparison has been made between the treatment effects of nedocromil sodium and placebo, using six efficacy variables (day and night asthma, cough, mean daily peak expiratory flow rate, inhaled bronchodilator use, clinic lung function (forced expiratory volume in one second) and global opinion of treatment efficacy. One hundred and twenty seven trial centres, involving 4,723 patients, have been included. The results demonstrate the efficacy of inhaled nedocromil sodium in a variety of patients with asthma. Optimal effects are evident in patients with moderate asthma, currently receiving treatment with inhaled and oral bronchodilators.
Haemorrhagic pleural effusion several months after inhalation of a foreign body
Authors: Steffensen I , Faurschou P
Published: November 2022

We present the case of a 50 yr old female with chronic obstructive lung disease, who, secondary to inhalation of a foreign body, developed recurrent pneumonia and a haemorrhagic pleural effusion (HPE). The foreign body (vegetable matter) was removed by rigid bronchoscopy and the patient recovered.
Alveolar haemorrhage as a presenting feature of myeloma
Authors: Russi E , Odermatt B , Joller-Jemelka HI , Spycher MA
Published: November 2022

An immunoglobulin A (IgA)-paraprotein secreting myeloma was found to be the underlying disease in a patient who presented with alveolar haemorrhage. The diffuse pulmonary bleeding stopped after initiation of treatment consisting of corticosteroids and melphalan. A paraprotein mediated lesion of the alveolar capillary membrane was suspected but could not be demonstrated.
Effect of frusemide on bradykinin- and capsaicin-induced contraction of the guinea-pig trachea
Authors: Molimard M , Advenier C
Published: November 2022

Frusemide, a loop diuretic, inhibits the bronchial response to various bronchoconstrictor stimuli in asthmatic subjects. The underlying mechanisms remain unclear. In order to determine whether frusemide inhibits pharmacologically induced C-fibre stimulation, we investigated the effect of frusemide on bradykinin-, capsaicin-, neurokinin A-, and substance P-induced contraction of the guinea-pig isolated trachea. Frusemide 10(-5) and 10(-4) M produced a significant inhibition of concentration-response curves to bradykinin, which was markedly reduced by indomethacin 10(-6) M. Frusemide significantly reduced capsaicin-induced contraction only in the presence of indomethacin 10(-6) M. Neurokinin A- and substance P-induced contractions were not affected by frusemide and/or indomethacin. Our data suggest that a cyclo-oxygenase pathway is involved in the inhibition by frusemide of the bradykinin-induced contraction, but not in the inhibition of the capsaicin-induced contraction.