bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive pleural inflammation caused by intratracheal instillation of killed microbes
Authors: Li XY , Brown GM , Lamb D , Donaldson K
Published: November 2022

To investigate the pleural leucocyte response to severe alveolar inflammation, heat-killed Corynebacterium parvum were instilled intratracheally into the lungs of PVG rats and pleural lavage was performed. Polymorphonuclear neutrophils are not normally resident in the pleural space but were found transiently after intratracheal instillation of C. parvum. Macrophages increased gradually in the pleural space following instillation, reaching a peak at day 5. The activity of plasminogen activator inhibitor in the pleural leucocyte supernatants was increased at day 1, but returned to control levels by day 5. The activities of interleukin-1 and tumour necrosis factor secreted by pleural leucocytes were decreased compared with control pleural leucocytes at day 1 and were further reduced at day 5. The analysis of particle translocation showed that intratracheally instilled C. parvum and fluorescent beads with or without C. parvum did not reach the pleural space. We hypothesize that pleural inflammation resulting from C. parvum-induced inflammation in the lung is the result of transfer of a diffusible factor from the adjacent parenchyma.
Influence of in vivo prednisolone on increased in vitro O2- generation by neutrophils in emphysema
Authors: Renkema TE , Postma DS , Noordhoek JA , Sluiter HJ , Kauffman HF
Published: November 2022

Evidence is accumulating that neutrophil-derived oxidants substantially contribute to the development of emphysema, especially in smoking individuals. It is not clear, however, why not all smokers develop emphysema. We tested the hypothesis that an abnormality in the oxidative metabolism of polymorphonuclear leucocytes (PMNs) might contribute to the development of emphysema. We investigated in vitro O2- production by peripheral PMNs in patients with stable emphysema and in healthy controls. In addition, we investigated whether in vivo prednisolone may modulate in vitro O2- production by PMNs in patients with emphysema during a stable phase of the disease. Spontaneous O2- production by PMNs was not significantly different in patients and controls. After stimulation with submaximal concentrations of calcium ionophore A23187 and phorbol myristate acetate, however, PMNs from patients with stable emphysema produced more O2- than those from healthy controls, especially in smoking subjects. Moreover, in vitro O2- generation by PMNs significantly decreased after in vivo prednisolone treatment in patients with emphysema. We suggest that our findings reflect an abnormality of PMNs, acting as one of the factors that contribute to the development of emphysema. This abnormality may, at least partially, be dampened by in vivo prednisolone treatment. These findings may provide new insights into the pathogenesis and treatment of pulmonary emphysema. Further studies on pulmonary PMNs are necessary to extend our findings.
Reversibility of exogenous corticosteroid-induced bone loss
Authors: Rizzato G , Montemurro L
Published: November 2022

Osteoporosis is not usually considered to be reversible, as it is a consequence of the ageing process. However, an improvement of bone mineral density after successful surgery in Cushing's syndrome has been shown in several reports. The question of reversibility of exogenous corticosteroid-induced osteoporosis is, as yet, unanswered, possibly because of the difficulty in discontinuing steroids after long-term use. We describe six patients, all under 45 yrs of age, with chronic long-standing sarcoidosis, in whom long-term prednisone therapy resulted in 15 +/- 7% bone loss, as evaluated by quantitative computed tomography. This side-effect appeared fully reversible after prednisone withdrawal. This report of the reversibility of exogenous corticosteroid-induced bone loss needs confirmation in elderly people, where the capacity for recovery of bone mass could be reduced. Such potential for recovery may have implications for the pattern of use of corticosteroids.
Vascular volume expansion and thermally induced asthma
Authors: Gilbert IA , Winslow CJ , Lenner KA , Nelson JA , McFadden ER
Published: November 2022

To determine whether a relationship exists between intravenous infusion of isotonic fluid and reactivity to hyperpnoea, eight normal and eight asthmatic subjects underwent rapid intravascular administration of approximately 2 l of warm normal saline, by itself and before and after hyperventilation of cold air. In the asthmatic subjects, saline infusion mirrored the obstruction seen with hyperventilation; whereas, in normal subjects saline produced more bronchial narrowing than hyperventilation. When the two stimuli were given together, the timing of the infusion altered the asthmatic subjects' responses. Giving fluid early in the hyperventilation challenge blunted obstruction, whereas giving it later amplified the airway narrowing. Similar findings, but on a smaller scale, occurred in normal subjects. These data demonstrate that sudden elevations in intrathoracic vascular volume with warm saline produce airway obstruction that is quantitatively similar to that seen with hyperventilation in asthmatic individuals. They also demonstrate that these two stimuli interact together in such a manner that a common mechanism may exist to account for the decrease in airflow.
Differences in utilization of asthma drugs between two neighbouring Swedish provinces: relation to symptom reporting
Authors: Larsson L , Boethius G , Uddenfeldt M
Published: November 2022

Utilization of anti-asthma drugs is rapidly increasing and varies markedly between counties in Sweden. In 1989, the sales in the county of Gavleborg were less than 60% of those in neighbouring Jamtland. In order to study the possible reasons for--and effects of--this difference, an epidemiological survey was started in 1989, the first part of which is reported here. A questionnaire was sent to all 16 yr olds, and to a random sample of 30-39 and 60-69 yr olds, in the two counties. A total of 12,500 questionnaires were distributed. Overall response rate was 90%. A total of 7.2% in Jamtland and 5.8% in Gavleborg (p < 0.01) reported that they had had asthma at some time. A similar significant difference between the counties was also present in response to questions on attacks of shortness of breath, wheezing and self-reported diagnosis of asthma, as well as on use of anti-asthma drugs. There were no statistically significant differences between the counties in positive answers to questions concerning history and symptoms of chronic bronchitis; approximately 5% in the oldest age group. The findings support earlier results indicating a high asthma prevalence in northern Sweden. Contrary to reports from other countries, the prevalence was higher in the colder and less urbanised of the two provinces. We conclude that the differences in drug sales between the counties reflect a difference in prevalence of asthmatic symptoms.
The large lungs of elite swimmers: an increased alveolar number?
Authors: Armour J , Donnelly PM , Bye PT
Published: November 2022

In order to obtain further insight into the mechanisms relating to the large lung volumes of swimmers, tests of mechanical lung function, including lung distensibility (K) and elastic recoil, pulmonary diffusion capacity, and respiratory mouth pressures, together with anthropometric data (height, weight, body surface area, chest width, depth and surface area), were compared in eight elite male swimmers, eight elite male long distance athletes and eight control subjects. The differences in training profiles of each group were also examined. There was no significant difference in height between the subjects, but the swimmers were younger than both the runners and controls, and both the swimmers and controls were heavier than the runners. Of all the training variables, only the mean total distance in kilometers covered per week was significantly greater in the runners. Whether based on: (a) adolescent predicted values; or (b) adult male predicted values, swimmers had significantly increased total lung capacity ((a) 145 +/- 22%, (mean +/- SD) (b) 128 +/- 15%); vital capacity ((a) 146 +/- 24%, (b) 124 +/- 15%); and inspiratory capacity ((a) 155 +/- 33%, (b) 138 +/- 29%), but this was not found in the other two groups. Swimmers also had the largest chest surface area and chest width. Forced expiratory volume in one second (FEV1) was largest in the swimmers ((b) 122 +/- 17%) and FEV1 as a percentage of forced vital capacity (FEV1/FVC)% was similar for the three groups. Pulmonary diffusing capacity (DLCO) was also highest in the swimmers (117 +/- 18%). All of the other indices of lung function, including pulmonary distensibility (K), elastic recoil and diffusion coefficient (KCO), were similar. These findings suggest that swimmers may have achieved greater lung volumes than either runners or control subjects, not because of greater inspiratory muscle strength, or differences in height, fat free mass, alveolar distensibility, age at start of training or sternal length or chest depth, but by developing physically wider chests, containing an increased number of alveoli, rather than alveoli of increased size. However, in this cross-sectional study, hereditary factors cannot be ruled out, although we believe them to be less likely.
L-arginine-dependent nitric oxide synthase: a new metabolic pathway in the lung and airways
Authors: Jorens PG , Vermeire PA , Herman AG
Published: November 2022

An L-arginine-dependent pathway, metabolising L-arginine to citrulline and nitrogen oxides, has been described in many cell types in different species, including man. Two subtypes of this nitric oxide synthase have been reported: a constitutive enzyme type, releasing nitric oxide after stimulation, is typically found in endothelial and neural cells; another subtype can be induced in macrophages after cytokine treatment. This review summarizes the literature on the known and proposed roles of this L-arginine-dependent nitric oxide production in different pulmonary processes. Nitric oxide has been reported to act as a neurotransmitter in the inhibitory nonadrenergic, noncholinergic nerves in the airways of guinea-pig and man. It is released in cytostatic processes by immune-stimulated alveolar macrophages. Recent data on the role of L-arginine-dependent processes in immune-complex-mediated lung injury, histamine-induced activation of guanylate cyclase or cytokine networks in the lung are also discussed. Finally, similarities and differences between tracheal epithelium-derived relaxing factor and nitric oxide are analysed. The details of the role and distribution of nitric oxide synthase in the (human) lung and airways are not yet completely understood. Nitric oxide is believed to play a role in various pulmonary physiological processes, such as bronchodilation and the cytotoxic action of certain cells. The modulation of nitric oxide release will therefore, most probably lead to application of novel therapies in diseases such as asthma and inflammatory pulmonary diseases.
Pancoast syndrome: an unusual presentation of adenoid cystic carcinoma
Authors: Hatton MQ , Allen MB , Cooke NJ
Published: November 2022

We report on a patient with primary pulmonary adenoid cystic carcinoma presenting with Pancoast syndrome. Pancoast syndrome has not previously been described with this tumour. Other unusual features of this case include the peripheral origin and mediastinal involvement, with lack of proximal endobronchial spread.
Vital prognosis in intrathoracic sarcoidosis with special reference to pulmonary function and radiological stage
Authors: Viskum K , Vestbo J
Published: November 2022

A follow-up of 254 patients with intrathoracic sarcoidosis has been carried out after a median of 27 yrs from the diagnostic admission. All patients could be traced. At the end of follow-up there was no excess mortality (80 deaths observed versus 65.5 expected). However, during the first 20 yrs of follow-up a slight excess mortality was seen. Thirty three out of the 80 deaths were related to sarcoidosis. No excess number of deaths from lung cancer or lymphoma was observed. Erythema nodosum was of no prognostic significance concerning survival. X-ray stage was related to survival with a significant excess mortality for stage 3. Early clearing of X-ray changes gave a favourable vital prognosis. Survival was related to lung function, and for forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) index and total lung capacity (TLC) this relationship reached levels of statistical significance. In multivariate Cox regression models, with age and sex entered as covariates, the same parameters were found to be significant predictors of mortality. Patients with FEV1 < or = 50% predicted had an increased mortality risk of 4.2 (95% confidence interval 1.8-9.6) when compared to patients with FEV1 > 80% predicted. Likewise, patients with TLC < or = 80% predicted had a mortality risk of 2.6 (1.5-4.5) when compared to patients with TLC > 80% predicted. In conclusion, a modest excess mortality was observed during the first 20 yrs of follow-up. Furthermore, both X-ray staging and lung function at the time of diagnosis influenced long-term mortality in patients with intrathoracic sarcoidosis.
Acute exposure to swine dust causes bronchial hyperresponsiveness in healthy subjects
Authors: Malmberg P , Larsson K
Published: November 2022

Six urban subjects, with little or no previous experience of farm-work, were exposed to dust while weighing swine for 2-5 h. Three subjects experienced toxic symptoms 4-5 h after the beginning of exposure. Bronchial responsiveness increased in all subjects within 6 h (more than three doubling steps difference in a methacholine test). One week later, airway responsiveness had partly normalized. The mean (interquartile range) cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV1) was 3.1 (1.0-6.6) mg, before exposure, fell to 0.13 (0.01-0.76) mg 6 h after exposure (p < 0.02), and was 0.99 (0.42-1.5) mg one week later (n = 5, p < 0.05), Mean (SD) FEV1 decreased 5 (2)%. The concentration of total dust varied between 9 and 14 mg.m-3 and of endotoxin between 0.1 and 0.5 mu g.m-3. Thus inhalation of swine farm dust, caused a marked increase in bronchial responsiveness in non-sensitized subjects.
Nonadrenergic, noncholinergic responses stabilize smooth muscle tone, with and without parasympathetic activation, in guinea-pig isolated airways
Authors: Linden A , Lofdahl CG , Ullman A , Skoogh BE
Published: November 2022

In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The mean level of the tonus equilibrium (% of maximum tone) was higher with the simultaneous NANC and parasympathetic activation than with NANC activation alone (75% compared with 44%, in the main bronchus, n = 8). The level of the tonus equilibrium was also higher with the simultaneous NANC, sympathetic and parasympathetic activation than with NANC and sympathetic activation only (49% compared with 21%, in the main bronchus, n = 8). The pattern was similar in the distal trachea. In conclusion, NANC neural responses can stabilize smooth muscle tone, and this stabilizing effect can be modulated by both parasympathetic and sympathetic activation, in guinea-pig isolated airways.
Inhalation challenge in pigeon breeder's disease: BAL fluid changes after 6 hours
Authors: Reynolds SP , Jones KP , Edwards JH , Davies BH
Published: November 2022

The purpose of this study was to determine the cellular events occurring 6 h after bronchial inhalation challenge, in a group of pigeon breeders. Twelve subjects agreed to undergo challenge, either with nebulized pigeon serum (Ps) (n = 10), or with saline (n = 2). The development of characteristic symptoms was used to detect a positive response in combination with monitoring tests (white blood cell count (WBC), body temperature, and spirometry). An initial bronchoalveolar lavage (BAL) was performed before inhalation challenge, and a further BAL on the previously spared right middle lobe subsegment or lingula 6 h after challenge. Paired bronchoalveolar lavage fluid (BALF) samples were analysed for urea, albumin, total and differential WBC, interleukin-1 and interleukin-2. There was a significant increase in total cells, lymphocytes, T-lymphocytes, and neutrophils; numbers.ml-1 of BALF in responders. A monitoring score reflecting severity of patient response correlated with an increase in all cell types (p < 0.05). In conclusion, responders developed both a BALF lymphocytic and neutrophilic "alveolitis" following inhalation challenge, the degree of BALF "alveolitis" correlating with the severity of patient response.
Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils
Authors: Polla BS , Kantengwa S , Gleich GJ , Kondo M , Reimert CM , Junod AF
Published: November 2022

Synthesis of heat shock proteins (HSPs) is induced in all cells and tissues after exposure to elevated temperatures, or a variety of other types of injury, including oxidative injury. We have previously reported that stress proteins are induced in monocytes-macrophages during phagocytosis of red blood cells. Receptor-mediated phagocytosis is associated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Similar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of proteins synthesized by human AMs recovered by bronchoalveolar lavage (BAL) in interstitial lung disease, both under basal conditions and after in vitro exposure to heat or hydrogen peroxide (H2O2). In two out of the 17 cases studied, we observed a high alveolar eosinophilia (10 and 24%, respectively) and phagocytosis, by the AMs, of eosinophilic material. Whereas exposure to heat or H2O2 induced in all AMs the synthesis of the classical HSPs, in these two cases, we found spontaneous synthesis of HSPs and of a 32 kD oxidation-specific stress protein, haeme oxygenase (HO). Exposure of AM to purified eosinophil-derived proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), alone or in combination, did not induce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may represent a new cellular marker of pulmonary injury and eosinophilic inflammation, and an autoprotective mechanism against oxidative stress.
Changes in bronchoalveolar lavage inflammatory cells in asthmatic patients treated with high dose inhaled beclomethasone dipropionate
Authors: Duddridge M , Ward C , Hendrick DJ , Walters EH
Published: November 2022

Using serial bronchoalveolar lavage (BAL), we have studied changes in the airway inflammatory cell populations in 20 asthmatic patients, before and after treatment with inhaled beclomethasone dipropionate (BDP), 2,000 micrograms daily in an uncontrolled study. There was a significant improvement in asthma severity, as measured by symptom score and airways responsiveness, and there were significant reductions in the total BAL eosinophil, epithelial cell and mast cell counts, with a significant increase in the percentage BAL lymphocyte count. No significant correlations were found between the changes in airway inflammatory cell numbers and the reduction in asthma severity. In contrast, the fall in ROS generation by the pulmonary macrophage and granulocyte populations was nonsignificant, but the improvement in airways responsiveness was positively correlated to the reduction in the unstimulated pulmonary macrophage activity. Although these data are uncontrolled, the results are compatible with previous studies in suggesting an effect of steroids on the eosinophil, mast cell and epithelial cell in asthmatic airways. They also highlight the probable importance of the luminal lymphocyte population and pulmonary macrophage activation within the asthmatic airway, the beneficial modulatory effect of inhaled BDP treatment upon them, and the relative steroid-resistance of pulmonary inflammatory cell activity.
Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children
Authors: Pistelli R , Forastiere F , Corbo GM , Dell'Orco V , Brancato G , Agabiti N , Pizzabiocca A , Perucci CA
Published: November 2022

To investigate whether dietary salt intake and urinary sodium and potassium levels are related to respiratory symptoms and bronchial responsiveness, a cross-sectional study among 2593 subjects aged 9 to 16 was conducted in four communities of the Latium region (Italy). Questionnaires were administered to the parents, urine samples were collected, lung function, methacholine challenge tests and prick tests were performed. Information about familial and personal dietary salt use and respiratory health was collected from the parents of 2439 (94%) subjects. A total of 2020 methacholine challenge tests and 916 urinary sodium and potassium levels were available for analysis. Personal table salt use was strongly related to cough and phlegm apart from colds (adjusted odds ratios, OR, 1.87, 95% confidence intervals, CI, 1.20-2.90), wheezing apart from colds (OR, 2.19, 95% CI, 1.27-3.77), wheezing with dyspnoea (OR, 1.45, 95% CI, 0.98-2.12) and wheezing after exercise (OR, 2.16, 95% CI, 1.35-3.44). These associations were mainly found in boys. Use of familial table salt and canned food showed no relation to respiratory symptoms. Increased bronchial responsiveness was associated with a higher urinary potassium excretion in boys, but not with urinary sodium. In conclusion, personal table salt use is related to an increased prevalence of bronchial symptoms; an increase in bronchial responsiveness among those with higher potassium excretion also seems to be implied. Although it is difficult to interpret the results of this study in causal terms, the findings might be relevant to the distribution of bronchial symptoms and diseases in the population.
Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children
Authors: Comis A , Valletta EA , Sette L , Andreoli A , Boner AL
Published: November 2022

To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG) administered by metered dose inhaler (MDI) in preventing exercise-induced asthma (EIA), 12 asthmatic children with EIA were studied in a randomized, double-blind, cross-over, placebo-controlled study. NS and SCG were given by MDI alone, and by MDI with a 700 ml spacer device (Fisonair, Fisons, UK), in order to assess the benefit of using such a device. Following a baseline exercise challenge, the protective effect of NS, SCG or placebo was evaluated in each subject. The percentage fall in forced expiratory volume in one second, and percentage protection were measured. NS and SCG provided a significant and comparable protection from EIA, and both were better than placebo. No further improvement was observed after drug administration via the spacer. Both NS and SCG are effective in preventing EIA in children, when administered at the recommended clinical dose, and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good.
No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study
Authors: Fuglsang G , Hertz B , Holm EB
Published: November 2022

We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate, in 17 asthmatic children aged 6-12 yrs (mean 9 yrs). Placebo, 2, 4 and 6 mg terbutaline were given b.i.d. for 14 days, in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline.day-1, respectively. There was no correlation between plasma terbutaline and dose of terbutaline. A small but statistically significant dose-related increase in morning and evening peak expiratory flow (PEF) recordings occurred, but the incidence of side-effects also increased with the dose given. There was a trend towards more side-effects when the high doses were used, and two patients withdrew from the study because of side-effects at this dose. It is concluded that continuous treatment, even with high doses of oral terbutaline, does not offer clinically useful protection against exercise-induced asthma.
Snoring, asthma and sleep disturbance in Britain: a community-based survey
Authors: Fitzpatrick MF , Martin K , Fossey E , Shapiro CM , Elton RA , Douglas NJ
Published: November 2022

A questionnaire was sent to a random sample of adults in eight locations throughout Britain, to investigate the prevalence of snoring, asthma and sleep complaints in community-based British adult. Of the 1,478 respondents (831 females, 647 males; mean +/- SD age 45 +/- 18 yrs), 37% reported snoring at least occasionally, and 11% reported snoring on at least four nights per week (frequent snorers). Frequent snorers reported spending less time asleep at night, falling asleep accidentally during the day more often, taking planned daytime naps, and falling asleep whilst driving or operating machinery more often than the other respondent. Using ordinal logistic regression analysis to allow for the age and sex of the respondents, both accidental daytime sleep and planned daytime naps were commoner in frequent snorers than other respondents. Six percent of all respondents and 6% of those aged under 40 yrs reported that they had asthma (asthmatics). Seven percent of respondents aged less than 40 yrs reported wheezing on three or more occasions per year, and had been prescribed oral or inhaled bronchodilators (young wheezers). More than 80% of the asthmatic respondents of all ages, and young wheezers, reported waking at night with wheeze at least occasionally, and more than 30% of each group reported this symptom frequently. A larger proportion of asthmatics and young wheezers reported that their night-time sleep was unrefreshing, and that they had too little sleep at night than the other respondents.(ABSTRACT TRUNCATED AT 250 WORDS)
Value of pulse oximetry in screening for long-term oxygen therapy requirement
Authors: Roberts CM , Bugler  , Melchor R , Hetzel MR , Spiro SG
Published: November 2022

Pulse oximetry, combined with spirometry, was evaluated as a method of selecting chronic obstructive pulmonary disease (COPD) out-patients requiring definitive arterial blood gas analysis for long-term oxygen therapy (LTOT) assessment. A relatively high screening arterial oxygen saturation by pulse oximetry (SaO2) level was set, in order to maximize sensitivity. All 113 COPD out-patients attending the hospital clinic over a 6 month period were screened. Sixty had a forced expiratory volume in one second < 1.5 l and 26 had an SaO2 < or = 92%. These 26 underwent arterial blood gas analysis. Nine had an arterial oxygen tension < 7.3 kPa all with an arterial carbon dioxide tension (PaCO2) > 6 kPa. A further eight had a PaO2 < 8 kPa. This produced a sensitivity of 100% and specificity of 69% for oximetry in the detection of PaO2 < 7.3 kPa determined by direct arterial puncture and 100% and 86% respectively for detecting a PaO2 < 8 kPa. Although the poor specificity of oximetry in the crucial PaO2 range makes it unsuitable, when used alone, for prescription of LTOT, it may prove valuable in selecting patients who require further definitive arterial blood gas analysis.
Respiratory response to CO2 in patients with chronic obstructive pulmonary disease in acute respiratory failure
Authors: Tardif C , Bonmarchand G , Gibon JF , Hellot MF , Leroy J , Pasquis P , Milic-Emili J , Derenne JP
Published: November 2022

The aim of our study was to determine the importance of chemoreceptor stimulation by carbon dioxide in setting the level of ventilation in patients with chronic obstructive pulmonary disease (COPD) in acute respiratory failure. We studied the ventilatory and mouth occlusion pressure (P0.1) responses to CO2 in 25 COPD patients under treatment for episodes of acute respiratory failure, and in 24 normal subjects. Carbon dioxide rebreathing tests were performed in the spontaneously breathing, intubated patients, after arterial blood gases had been quasi-normalized by mechanical ventilation, which allowed us to compare both groups at similar resting arterial carbon dioxide tension (PaCO2) and acid-base status. The slopes of the ventilatory responses were markedly lower in the patients (mean +/- SEM, 1.28 +/- 0.23 versus 12.53 +/- 1.13 l.min-1.kPa-1). The slopes of the P0.1 responses were lower in the patients (0.27 +/- 0.05 versus 0.45 +/- 0.05 kPa.kPa-1), but the absolute P0.1 values were not significantly different from the normals. Increasing PaCO2 from 5.3 to 8 kPa (40 to 60 mmHg) resulted in a mean increase of 34% in ventilation. These results show that CO2 drive is a major determinant of respiratory stimulation in many COPD patients with acute respiratory failure.
The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group
Authors: Waalkens HJ , van Essen-Zandvliet EE , Gerritsen J , Duiverman EJ , Kerrebijn KF , Knol K
Published: November 2022

The effect of long-term treatment with inhaled corticosteroid on exercise-induced asthma (EIA) was studied in 55 children, aged 7-18 yrs (mean 12 yrs). We also compared the time course of stabilization of EIA to that of other indicators of airway responsiveness, such as peak expiratory flow (PEF) variation and the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1). All children participated in an ongoing multicentre study to compare the effects of long-term treatment either with the beta 2-agonist salbutamol (600 micrograms.day-1) plus the inhaled corticosteroid budesonide (600 micrograms.day-1) (BA+CS), or salbutamol plus placebo (BA+PL), on airway calibre, airway responsiveness and symptoms. After a median follow-up of 22 months, the study design had to be changed, because of the high number of drop-outs on BA+PL. At that time, the treatment regimen of all children who had not withdrawn was changed into BA+CS. At the moment of change, and after 2 and 8 months of treatment, a treadmill exercise test was performed in two centres. Eighteen of the 22 children (82%) who were treated with BA+PL from the beginning had EIA, compared to 18 of the 33 children (55%) who were treated with BA-CS (p < 0.05). After 2 and 8 months of treatment with BA+CS in the patients previously on BA+PL this percentage decreased to 59 and 55%, respectively, and was not significantly different between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies
Authors: Chinn S , Burney PG , Britton  , Tattersfield AE , Higgins BG
Published: November 2022

Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Daily home spirometry facilitates early detection of rejection in single lung transplant recipients with emphysema
Authors: Bjortuft O , Johansen B , Boe J , Foerster A , Holter E , Geiran O
Published: November 2022

Eight single lung transplant recipients with emphysema, aged 40-58 yrs, have been followed up for 90 patient months. Starting 2-4 weeks postoperatively, they recorded their forced vital capacity (FVC), and forced expiratory volume in one second (FEV1), at a fixed time every morning using a Micro Spirometer. They were instructed to contact the hospital if the FVC or FEV1 displayed a persistent (two days or more) decrease of 10%, compared with the average values during the last seven days. Transbronchial biopsies (TBB) were performed regularly in the follow-up, and whenever the patients had respiratory symptoms, or the FVC or FEV1 displayed a persistent decline of more than 10%. We performed 59 TBBs, and 23 biopsy specimens showed rejection. The FVC and FEV1 values on the TBB day were compared with the mean values of the 7 previous days. FVC and FEV1, associated with negative TBBs (16 events), showed no significant changes. However, FVC and FEV1 decreased significantly (p < 0.001, paired t-test) during rejections (mean percentage change 14 and 21% respectively, range +8% to -53%). In 16 of the 23 rejections, the FEV1 decreased by > 10%. We recommend the use of daily home spirometry when monitoring single lung recipients with emphysema, and suggest that a persistent 10% decrease in FEV1 or FVC for at least two days is an indication for hospital admission and possible TBB.
Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components
Authors: Teschler H , Thompson AB , Pohl WR , Konietzko N , Rennard SI , Costabel U
Published: November 2022

Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.
Recurrent interlobar pneumothorax in an asthmatic patient
Authors: Gourdon C , Dietemann A , Beigelman C , Sohier B , Pauli G
Published: November 2022

We report a case of spontaneous interlobar pneumothorax, an uncommon condition. The diagnosis was suspected from the frontal chest X-ray, which showed an incompletely circumscribed air-containing space, with a fluid level. The diagnosis was confirmed by the lateral projections of standard X-ray and tomography, and by thoracic computed tomography (CT). Such air-fluid levels should not be confused with pneumatocele, cystic or cavitary diseases.
Modelling of passive expiration in patients with adult respiratory distress syndrome
Authors: Chelucci GL , Dall' Ava-Santucci J , Dhainaut JF , Chelucci A , Allegra A , Paccaly D , Brunet F , Milic-Emili J , Lockhart A
Published: November 2022

The time-course of volume change during passive expiration preceded by an end-inspiratory hold was studied with a biexponential model in six adult respiratory distress syndrome (ARDS) patients. We measured the initial volumes and time constants of the fast (tau 1), and the slow (tau 2) compartments of expiration, as well as the static elastance of the respiratory system. The results were compared to those of 11 normal subjects. We observed that: 1) the biexponential model fitted closely the volume decay; 2) the fast compartment was responsible for 81 +/- 7% (ARDS) versus 84 +/- 10% (controls) of the total volume exhaled, with tau 1 = 0.35 +/- 0.11 s (ARDS) versus 0.50 +/- 0.22 s (controls); 3) the slow compartment contributed only 19 +/- 6% (ARDS) versus 16 +/- 7% (controls), with tau 2 = 4.67 +/- 2.38 s (ARDS) versus 3.27 +/- 1.54 s (controls); and 4) static elastance was higher in ARDS patients. The findings could be explained in terms of a four parameter viscoelastic model of the respiratory system.
Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis
Authors: Amicosante M , Paone G , Ameglio F , Bianchi EL , Piccolella E , Richeldi L , Bisetti A , Luisetti M , Saltini C
Published: November 2022

The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.
High prevalence of asthma and related symptoms in teenagers in northern Sweden
Authors: Norrman E , Rosenhall L , Nystrom L , Bergstrm E , Stjenberg N
Published: November 2022

Recent reports have suggested an increased asthma prevalence in the Nordic countries. The prevalence of asthma and related symptoms from lower airways in Umea, Northern Sweden, was investigated in 1987. We used a questionnaire and a skin prick test in 1,112 teenagers. Individuals with symptoms or positive skin prick tests were examined further. The clinical examination included an interview, a ventilatory lung function test, serum specific immunoglobulin E (IgE) test, and a physical examination. Individuals with symptoms from the lower airways underwent a methacholine inhalation test. Asthma was defined as recurrent attacks of dyspnoea and/or wheezing, triggered by known stimuli (excluding infections), and at least one of the following: signs of obstructive airways at examination or provocation concentration giving a 20% fall in forced expiratory volume in one second (PC20) < 8 mg.ml-1. Using this definition, the prevalence of asthma was 6.8%, with a significantly higher prevalence in girls (9.6%) than in boys (4.1%). Furthermore, 16.4% had dyspnoea, wheeze or prolonged cough but did not fulfil our criteria for asthma. The prevalence of asthma and of symptoms from lower airways is higher than has previously been found in Sweden.
Compliance with pulmonary medication in general practice
Authors: Dekker FW , Dieleman FE , Kaptein AA , Mulder JD
Published: November 2022

We wanted to assess compliance with regular pulmonary medication, in 156 patients in a general practice setting. Patients completed a questionnaire on their reported daily intake, the perceived prescription, and their self-assessed perceived compliance with pulmonary medication. Compliance was defined as a reported daily intake > or = 50% of the prescribed amount. Using this definition, 30% of patients were considered to be compliant. Compliant patients had daily symptoms more often, were more often prescribed two or more different medications, and a greater proportion of them had at some time consulted a chest physician. When patients correctly perceived the prescription to refer to medication which had to be taken on a regular basis, they were more likely to be compliant. We conclude that, since less than one third of patients was compliant with medication, more efforts are needed to improve compliance in general practice. Non-compliance with medication may well provide an alternative explanation for the discrepancy between prescribed medication and medical outcome, which has been labelled in the literature as "undertreatment".
Cellular and molecular mechanisms of bacterial adhesion to respiratory mucosa
Authors: Plotkowski MC , Bajolet-Laudinat O , Puchelle E
Published: November 2022

Different bacterial species adhere avidly to respiratory mucus. Such adhesion, when followed by ciliary clearance, represents an important stage of the airway defense system. However, in pathological conditions, the mucociliary clearance may be severely reduced, and mucus-associated bacteria may multiply and infect the underlying epithelium. Only a few bacteria have been shown to adhere to ciliary membranes of functionally active ciliated cells. Therefore, the first way in which most of the respiratory pathogens associate with the airway epithelium is likely to be by their adhesion to mucus. Some bacteria also secrete products that may affect ciliary function and/or cause cell death and epithelial disruption. Respiratory pathogens that do not bind to normal ciliated cells may readily adhere to injured epithelial cells, or to the unmasked extracellular matrix. Furthermore, following injury, epithelial respiratory cells in the process of migration, in order to repair the wounds, may present receptors to which bacteria adhere. The adhesion to all of these epithelial receptors may contribute to the chronicity of many bacterial respiratory infections.
Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease
Authors: Pforte A , Gerth C , Voss A , Beer B , Haussinger K , Jutting U , Burger G , Ziegler-Heitbrock HW
Published: November 2022

In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease.
Pulmonary hypertension in childhood
Authors: Haworth SG
Published: November 2022

In the presence of pulmonary hypertension, the pulmonary vasculature fails to remodel after birth. Secondary changes then develop, and do so more rapidly than in the adult lung because the cells are exposed to the insult whilst still relatively undifferentiated. The commonest causes of pulmonary hypertension in newborn and young infants are alveolar hypoxia, and congenital heart disease causing a left-to-right shunt and increased pulmonary blood flow. The initial response of an increase in pulmonary arterial muscularity is common to both, but intimal proliferation can develop rapidly in those with complex congenital heart disease. The structural abnormalities are accompanied by abnormalities in the control of pulmonary vascular reactivity, a problem which is the focus of much current research activity.
Lesions of the arytenoid region in a patient with exertional dyspnoea
Authors: Nagai A , Matsumiya H , Hayashi M , Kanemura T , Yasui S , Konno K
Published: November 2022

A 63 year old woman presented with a 3 year history of exertional dyspnoea. Spirometry suggested extrathoracic airway obstruction (decreased inspiratory flow and saw-tooth pattern of flow-volume curves), and bronchoscopy revealed structural lesions and a trembling motion in the arytenoid region, causing upper airway obstruction on forced respiratory efforts. As there were no abnormal findings other than the lesions, the exertional dyspnoea was probably caused by impaired movement of the arytenoid region.