bluuebunny/crossref_metadata_2025 huggingface dataset:
A population survey of respiratory symptoms in the elderly
Authors: Dow L , Coggon D , Osmond C , Holgate ST
Published: November 2022

Reversible airways obstruction is not uncommon in the elderly, but may be overlooked because of the high prevalence of other disorders with a similar presentation. In a search for patterns of symptoms which might predict treatable airways obstruction, we carried out a survey of men and women aged 65 yrs and over. Postal questionnaires were completed by 2,161 subjects selected at random from the lists of three general practices. Almost 60% of the sample complained of one or more respiratory symptoms. Smoking was a more important risk factor than age, sex or social class, and was associated particularly with wheeze, morning phlegm and chest tightness on waking. Several groups of symptoms tended to cluster in the same individuals. The two most closely related were chest tightness and breathlessness in response to animals, dust and feathers. Responses to irritants tended to cluster according to the symptom produced (cough, breathlessness or wheeze) rather than the provoking stimulus (smoke, cold air, household chemicals or traffic fumes). There was no evidence for the existence of the "bronchial irritability syndrome" which has been linked with asthma in younger adults. The relationship of symptoms to respiratory function and bronchial reactivity will be reported in a further publication.
Lack of type II cells and emphysema in human lungs
Authors: Otto-Verberne CJ , Ten Have-Opbroek AA , Willems LN , Franken C , Kramps JA , Dijkman JH
Published: November 2022

Ten surgically removed human lungs or lobes were studied, to assess the relationship between the abundance of type II alveolar epithelial cells and the degree of emphysema. Type II cell abundance (total number as well as percentage of the total parenchymal cell population) was determined in sections of randomly selected tissue samples of these lungs or lobes by using a type II cell specific antibody specific anti-lavage serum (SALS-Hu), which recognizes surfactant-associated proteins. In these tissue samples we also determined the degree of emphysema with the aid of a number of morphometric parameters, destructive index (DI), mean linear intercept (Lm in mm), and the number of normal alveolar attachments on (pre)terminal bronchioles (normal AA.mm.1). We subsequently calculated the Spearman rank correlation coefficients (rs) between the abundance of type II cells and parameters for emphysema. We found a significant negative correlation between the percentage of type II cells and DI at tissue sample level (rs = 0.55; p = 0.02). We also calculated correlation coefficients between the abundance of type II cells and the degree of small airways disease in (pre)terminal and respiratory bronchioles (SADscore), lung function, age and smoking habits. The results suggest a role for type II cells in the pathogenesis of emphysema.
Two-compartment modelling of respiratory system mechanics at low frequencies: gas redistribution or tissue rheology?
Authors: Similowski T , Bates JH
Published: November 2022

The mechanical properties of the respiratory system are generally inferred from measurements of pressure and flow at the airway opening. Traditionally, these measurements have been related through a single-compartment model of the respiratory system. Recently, however, there has been considerable interest in modelling low-frequency respiratory mechanics in terms of two compartments, since this gives a much improved description of experimental data. In this paper we consider two classes of two-compartment models that are compatible with pressure-flow relationships of air measured at the airway opening. One type of model accounts for regional ventilation inhomogeneity in the lung in terms of two alveolar compartments. The other type of model considers pulmonary ventilation to be homogeneous, while the tissues of the respiratory system are modelled as being viscoelastic. In normal dogs, the appropriate two-compartment model has been shown to be the viscoelastic model. In the case of abnormal physiology, however, one must invoke a model having both viscoelastic tissues and ventilation inhomogeneities. Additional experimental data are required in order to identify such a model, and to quantify these two phenomena.
Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis
Authors: Higgins BG , Powell RM , Cooper S , Tattersfield AE
Published: November 2022

Bronchial reactivity to agonists such as histamine is seen in both chronic bronchitis and asthma, two conditions with different pathological changes in the airways. Salbutamol, when given acutely, reduces bronchial reactivity in patients with asthma, but the mechanism has not been clarified. To determine whether the effect of salbutamol depends on the pathological changes underlying the increased reactivity, we have compared the effect of salbutamol and ipratropium on bronchial reactivity in nine patients with asthma and ten with chronic bronchitis. Each drug was given on separate days in increasing doses (5, 100, 750, 1,000 micrograms) according to a double-blind, randomized design. Changes in forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured after each dose, and the provocative concentration of histamine causing a 20% fall in the FEV1 (PD20) was determined after the last dose. Salbutamol and ipratropium were equipotent in the asthmatic subjects and caused a similar maximal increase in FEV1 (0.58 and 0.57 l) and sGaw (0.166 and 0.154 s-1.kPa-1). The two drugs also produced similar changes in the patients with chronic bronchitis, although the maximum response to both drugs was smaller (FEV1 0.29 and 0.32 l; sGaw 0.056 and 0.060 s-1.kPa-1; p less than 0.05). Despite differences in bronchodilatation the increase in histamine PD20 following salbutamol was similar in the asthmatic and bronchitic subjects (2.26 and 1.90 doubling doses (DD)) and greater in both groups (p less than 0.05) than the change in PD20 with ipratropium (0.84 and 0.56 DD).(ABSTRACT TRUNCATED AT 250 WORDS)
Drug-induced lung disease: 1990 review
Authors: Israel-Biet D , Labrune S , Huchon GJ
Published: November 2022

Numerous drug-induced pulmonary manifestations have been reported but studies of their pathogenic mechanisms are still rare. These mechanisms should, however, be precisely determined in order to identify subjects at risk and to prevent some of these complications by the proper use of certain drugs in more appropriate conditions. The possibility of an iatrogenic manifestation should always be considered in patients developing pulmonary symptoms. Data from biological investigations, although not specific, contribute to the understanding of lung injury mechanisms.
A "splitting" look at chronic nonspecific lung disease (CNSLD): common features but diverse pathogenesis
Authors: Vermeire PA , Pride NB
Published: November 2022

The term chronic nonspecific lung disease (CNSLD) was proposed by the Ciba Symposium in 1959 as an umbrella term grouping chronic bronchitis, asthma, emphysema and irreversible or persistent obstructive lung disease. However, it has only been widely used by proponents of the Dutch Hypothesis, which states that these diseases all result from a common genetic root and should be considered as one disease. A major reason for proposing this hypothesis in 1961 was that these different entities share some common features, especially airway hyperresponsiveness. Although not formally disproven, evidence is accumulating--and reviewed here--against this "one disease concept"; hence, common features should not necessarily imply a common pathogenesis. Overlap features are sufficiently frequent in clinical practice to cause problems for labelling patients within the scope of CNSLD. The term could still be used as a starting point for a "splitting approach", identifying a small number of important basic features in order to allow a more systematic use of established labels for diseases within CNSLD. Our proposal for labelling emphasizes a consistent use of asthma, emphysema and chronic obstructive pulmonary disease (COPD), but restricts the use of chronic bronchitis to those patients with chronic bronchial hypersecretion without chronic airways obstruction.
A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects
Authors: Knox AJ , Wisniewski A , Cooper S , Tattersfield AE
Published: November 2022

Bronchial reactivity is being measured with increasing frequency in epidemiological studies, but there debate continues about the relative merits of the different methods used to measure reactivity, particularly for subjects with no previous experience of reactivity testing as is the case in epidemiological studies. Repeatability is likely to improve with practice, and laboratory based studies on experienced subjects may overestimate the repeatability of a test in inexperienced subjects. We have compared the repeatability of the Yan method with a dosimeter (Mefar) method of administering methacholine to 40 asthmatic subjects: 20 with experience of methacholine challenge on at least six previous occasions and 20 with no previous experience. Subjects attended the laboratory on four days within a two week period, at the same time of day. A methacholine challenge was performed on two occasions using the Yan method and on two occasions using the dosimeter. Methacholine responsiveness was measured as the provocative dose causing a 20% reduction in forced expiratory volume in one second (PD20FEV1). Geometric mean PD20FEV1 values with the Yan method were 1.14 doubling doses (DD) of methacholine higher than with the dosimeter method. In the experienced subjects, the 95% range for a single estimate was +/- 1.56 DD for the Yan method and +/- 1.37 DD for the dosimeter method. In the inexperienced subjects, the 95% ranges were +/- 2.65 and +/- 1.87 DD for the Yan and dosimeter methods, respectively. Thus, the differences in repeatability between the Yan and dosimeter methods, were small; experienced subjects gave more repeatable values than inexperienced subjects.
Neutrophil function in chronic bronchitis
Authors: Venge P , Rak S , Steinholtz L , Hakansson L , Lindblad G
Published: November 2022

This study was initiated with the question: Do defects in neutrophil functions predispose patients with chronic bronchitis to their recurrent bacterial infections? Forty five patients with chronic bronchitis and recurrent bacterial infections were studied. A number of aspects of neutrophil functions reflecting migratory and phagocytic functions and oxidative metabolism were measured in vitro, once in all 45 patients and 3 times in 22 patients over a period of 6 months. A great number of abnormalities was found on the first occasion with a complete normalization for all variables except one at the end of the observation period. The number of infectious exacerbations was significantly higher (p less than 0.05) at the start of the observation period i.e. October-November, as compared to the end, i.e. April-May. The oxidative metabolism, as reflected by lucigenin-enhanced chemiluminescence, was significantly reduced (p less than 0.001) also at the period of few infections, suggesting a primary defect of the neutrophil. Smoking was shown to adversely affect luminol-enhanced chemiluminescence and the chemokinetic activity of the patients' cells. We conclude that most variables were altered in a way which was anticipated from the study of individuals with acute bacterial infections. The probable primary defect in oxidative metabolism of the neutrophils in addition to the acquired defects as a consequence of smoking may add to the predisposition of some individuals to their recurrent bacterial infections.
Possible roles of the peripheral vagal nerve in histamine-induced bronchoconstriction in guinea-pigs
Authors: Inoue H , Aizawa H , Miyazaki N , Ikeda T , Shigematsu N
Published: November 2022

Although the importance of the vagal nerve in the pathogenesis of bronchial asthma has been reported, its precise contribution is still not fully understood. To shed more light on this area, we evaluated the possible contribution of vagal reflex in histamine-induced bronchoconstriction (HIB), and decided the site of action of histamine on the vagal nerve. For this purpose, we studied the effects of the bilateral cervical vagotomy, hexamethonium (2 mg.kg-1) or tetrodotoxin (0.5 mg.kg-1) on HIB (8 micrograms.kg-1, iv) in anaesthetized and mechanically-ventilated guinea-pigs. We also studied whether or not atropine (1 mg.kg-1) decreases HIB after vagotomy, including either the treatment of hexamethonium or tetrodotoxin. Airway responses were assessed by measurement of pulmonary resistance. The following results were obtained; 1) the response to histamine was significantly enhanced by the vagotomy, hexamethonium or tetrodotoxin; 2) propranolol increased HIB, and HIB was further enhanced by the vagotomy in the animals treated with propranolol; 3) atropine significantly suppressed HIB after the vagotomy, hexamethonium or tetrodotoxin. These results suggest that the postganglionic vagal nerve plays an excitatory role in HIB through the release of acetylcholine from the nerve terminals. It is also suggested that the vagal reflex mainly exhibits an inhibitory role in the HIB of guinea-pigs, presumably by the action of the nonadrenergic inhibitory nervous system.
Effort and dyspnoea during work of varying intensity and duration
Authors: Kearon MC , Summers E , Jones NL , Campbell EJ , Killian KJ
Published: November 2022

This study quantified the separate contributions of the intensity of exercise and its duration to muscular effort and dyspnoea during cycle ergometry. Six normal subjects estimated the perceived intensity (Borg scale 0-10) of peripheral muscular effort and dyspnoea during incremental exercise to their maximum work capacity (Wcap). On separate days, the same subjects exercised to endurance or 60 min at work rates rated for leg effort on the initial incremental test as: 2 ("slight", 33.1 +/- 1.45% Wcap) (mean +/- SE); 3 ("moderate", omission 83.6 +/- 3.87% Wcap). Perceived leg effort increased by a factor of 4.4 (2(2.13)) with a doubling of work rate and by 1.3 (2(0.39)) with a doubling of duration, as expressed by: Leg effort = k x %Wcap2.13 x Time0.39 (r2 = 0.87) Perceived dysponea increased 5.3-fold with a doubling of work rate and by 1.4-fold with a doubling of duration: Dysponea = k x %Wcap2.41 x Time0.47 (r2 = 0.75) Changes in work intensity, rather than duration, dominated symptom magnitudes such that in the performance of a given task, halving the intensity and doubling the duration of activity reduces the maximal intensity of muscular effort and dyspnoea to less than a third.
Bronchoalveolar lavage fibronectin in patients with sarcoidosis: correlation to hyaluronan and disease activity
Authors: Bjermer L , Eklund A , Blaschke E
Published: November 2022

Bronchoalveolar lavage was performed in 51 patients with sarcoidosis and in 21 healthy nonsmokers. The concentration of fibronectin was significantly higher (p less than 0.001) in lavage fluid from sarcoid patients (median 267 micrograms.l-1) than in that of controls (46 micrograms.l-1). Furthermore, a significantly higher concentration of fibronectin was found in patients with active disease than in those in whom the disease was inactive (p less than 0.001). In a six month follow-up perspective, patients with a progressive disease course had significantly higher levels of fibronectin than those who had a stable or regressive disorder (p less than 0.01). Correspondingly, lavage hyaluronan was higher (p less than 0.001) in sarcoid patients (55 micrograms.l-1) than in controls (9 micrograms.l-1) and higher (p less than 0.01) in those with active than in those with inactive disease. Patients with progressive disease had higher (p less than 0.01) concentrations of hyaluronan than those in whom the disease was stable. A significant correlation was found between lavage fibronectin levels and hyaluronan (r = 0.81, p less than 0.001). The percentage of mast cells was also higher in patients with active than in those with inactive disease (p less than 0.01) and higher in progressive than in stable sarcoidosis (p less than 0.001). Ten out of 10 patients with progressive disease had mast cells greater than or equal to 0.5%, hyaluronan greater than or equal to 50 micrograms.l-1 and fibronectin greater than or equal to 350 micrograms.l-1 compared to eight out of 41 patients with stable or regressive disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Lobar hypoplasia
Authors: Della Pona C , Rocco G , Rizzi A , Robustellini M , Rossi G , Crasti B
Published: November 2022

Lung tissue developmental abnormalities are seldom reported. According to the classification of Schneider (1900), which was amended by Boyden (1955), they include pulmonary agenesis, aplasia and hypoplasia. Due to the early onset of symptoms, lung agenesis and aplasia are usually detected soon after birth. Conversely, lung or lobar hypoplasia may remain clinically silent for a long time. A single case of left lower lobe hypoplasia is reported. A recurring and unrelenting septic fever was the presenting symptom, whilst the radiological picture showed a left lower lobe consolidation. On the surgical specimen gross pathology revealed a lobar hypoplasia. At a short-term follow-up (nine months) the patient shows good overall condition, being free from further complications.
Salmeterol: a four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease
Authors: Dahl R , Earnshaw JS , Palmer JB
Published: November 2022

A total of 1,068 patients, aged 18-70 yrs, with mild to moderate reversible airways disease, were recruited into a multicentre, double-blind, parallel group study in 76 European centres. Following a 2 week run-in period, the 692 patients fulfilling the entry criteria were randomized to 4 weeks treatment with either salmeterol 12.5, 50 or 100 micrograms or placebo b.d. all given by pressurized inhaler, with assessments of symptoms and ventilatory lung function prior to dosing. All three doses of salmeterol had significant efficacy, manifested by increased morning and evening peak expiratory flow rate (PEFR) (by 35-59 l.min-1 and 11-38 l.min-1, respectively), by reduced diurnal variation in PEFR, and by reduced requirement for additional bronchodilator for symptomatic relief. These effects were dose-related. Daytime asthma symptoms and nocturnal awakenings were significantly reduced by salmeterol treatment, although these reductions were not dose-related. The incidence of adverse events was low. Pharmacologically predictable events (e.g. tremor) were more frequent after treatment with 100 micrograms b.d. than with placebo. On the basis of the efficacy and side-effect information, 50 micrograms b.d. is considered to be the optimum dose for the treatment of this group of asthmatics.
Classification of lung cancer: first experiences with the new TNM classification (4th edition)
Authors: Bulzebruck H , Drings P , Kayser K , Schulz V , Tuengerthal S , Vogt-Moykopf I
Published: November 2022

In January 1987, the 4th edition of the TNM classification for malignant lung tumours by the International Union Cancer (UICC) came into effect. Thus, for the first time, a uniform worldwide staging system for lung cancer became available. In order to validate the new TNM definitions for lung cancer the data of 3,000 patients were analysed prospectively. Several items were examined: 1) the agreement between clinically (TNM) and pathologically (pTNM) confirmed classification; 2) the value of the various diagnostic techniques estimating the pathologically confirmed classification; 3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classifications were identical in 64%; for lymph node involvement (N) the agreement was 48%; for distant metastases it was 90% and for the stages it was 55%. As for the primary tumour (T) the accuracy of radiography (59%) was nearly identical to computed tomography (58%). Both techniques were less precise in determining the extent of lymph node involvement (computed tomography 50%, radiography 43%, correct assessments). The statistically significant differences in prognosis for the various T-, N- and M-categories as well as for the stages could be confirmed. By the new 1987 TNM definitions (4th edition) for lung cancer international conformity became feasible as well as practical, and the improvement in its prognostic relevance provided, therefore, a more reliable basis for establishing guidelines for individual oncological concepts of therapy.
Effects of ligustrazine on the pressure/flow relationship in isolated perfused rat lungs
Authors: Oddoy A , Bee D , Emery C , Barer G
Published: November 2022

Ligustrazine, the synthesized principle of a Chinese herbal remedy shown previously to be a pulmonary vasodilator, was tested in chronically hypoxic and normal rats. Pressure/flow, (P/Q), relations were measured in isolated perfused lungs during normoxia, hypoxia and after reversal of hypoxic vasoconstriction by increasing doses of ligustrazine. P/Q lines were linear over a wide range and extrapolation to the pressure axis gave an intercept which was the effective downstream pressure for flow. In chronically hypoxic rats the slope of the line was steeper and the intercept greater than in control rats, which we attributed to newly muscularized arterioles with tone. Hypoxia caused an increase in slope and intercept in both groups but the intercept increase was greater in chronically hypoxic rats. In both groups of rats increasing doses of ligustrazine given during continued hypoxia caused a fan of lines which moved progressively towards the control normoxic line. In chronically hypoxic rats it required only 2 mg of ligustrazine to bring the line back to the normoxic position, whereas in controls it required 4 mg. In chronically hypoxic rats the change in intercept with every dose was greater than in control rats; this suggests that ligustrazine mainly relaxes the muscle of small collapsible vessels. The action of ligustrazine remained in both control and chronically hypoxic rats after administration of an arginine analogue which blocks synthesis of the endothelial relaxant factor nitric oxide. This and previous evidence suggest that ligustrazine is a non-endothelial-dependent pulmonary vasodilator.
In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects
Authors: Renkema TE , Postma DS , Noordhoek JA , Sluiter HJ , Kauffman HF
Published: November 2022

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.
Neutrophil-endothelial cell interaction: evidence in vitro for a regulation by endothelial cells of neutrophil functions
Authors: Lassalle P , Delneste Y , Gosset P , Wallaert B , Tonnel AB , Dessaint JP , Capron A
Published: November 2022

The purpose of this study was to investigate a possible relationship between human umbilical vein endothelial cells (EC) triggered by ionophore A23187 at different doses (0.5-2.5 microM) and polymorphonuclear neutrophils (PMN). EC supernatants were shown to contain neutrophil chemoattractant activity (NCA) and in parallel a factor inducing an inhibition of PMN chemiluminescence (PMN CL). Supernatants obtained from EC triggered by A23187 exhibited a high level of NCA (73 +/- 5 PMN.hpf-1 compared to 21 +/- 4 PMN.hpf-1 in untreated EC supernatants, p less than 0.01). This NCA was independent from arachidonic acid metabolites, since indomethacin and nordi-hydroguaiaretic acid failed to suppress the chemotactic activity. Using gel filtration chromatography (AcA 54) the NCA was recovered in a single peak of apparent molecular weight of 37,000 +/- 4,000 daltons. Checkerboard analysis indicated that NCA exhibited both chemotactic and chemokinetic activities. In addition, supernatants of A23187-stimulated EC, and at a lesser degree, supernatants of unstimulated EC, inhibited PMN CL induced by N-formyl-Methionyl-Leucyl-Phenylalanine (61% inhibition, p less than 0.05), and by A23187 itself (80% inhibition, p less than 0.01), but not that induced by phorbol-myristate-acetate. Indomethacin and protamine sulphate did not modulate this inhibitory activity. By contrast, EC-derived inhibitory activity was inhibited (50%) by an adenosine antagonist (8-phenyltheophylline), indicating a participation of adenosine in this inhibitory activity of PMN CL. These data suggest the possibility that activated endothelial cells could both enhance PMN migration and protect themselves against potential damaging effects of oxygen metabolites produced by PMN, particularly during transvascular migration.
Tuberculosis elimination in the countries of Europe and other industrialized countries
Authors: Clancy L , Rieder HL , Enarson DA , Spinaci S
Published: November 2022

The working group summarized the conclusions of the workshop with the intention of providing a guide for the preparation of national plans for tuberculosis elimination. The basic strategies that appear consistently effective are: 1. Direct government responsibility for diagnosis, treatment and prevention of tuberculosis (the government is responsible by law for assuring that tuberculosis is identified early, and that cure of the patients is achieved). 2. Maintenance (or development) of properly designed disease surveillance and a programme monitoring system. 3. Availability of specialized tuberculosis personnel at regional and provincial level, responsible for close monitoring of the diagnostic skills and patient prioritization in general health institutions. Regarding research it was felt that no immediate practical applications of new techniques in the diagnosis of mycobacterial diseases, in treatment, or in vaccination can be recommended, but that further basic research in the field of mycobacteria should be pursued and supported.
Unilateral absence of a pulmonary artery: congenital disease or embolic occlusion?
Authors: Arriero JM , Gil J , Martin C , Mainar V , Romero S
Published: November 2022

A young man with congenital absence of the left pulmonary artery is reported. A right aortic arch and normal pulmonary pressures essentially rule out an alternate diagnosis of occlusive chronic thrombus in the central pulmonary arteries. Recurrent or massive haemoptysis makes an exact knowledge of the pulmonary circulation advisable.
Agenesis of the right pulmonary artery in a young asymptomatic girl
Authors: Morales P , Miravet L , Marco V
Published: November 2022

We report the case of a 13 yr old, asymptomatic girl with agenesis of the right pulmonary artery. In the context of a tuberculosis survey in her school, an X-ray examination disclosed a decreased volume of the right lung. Ventilation and perfusion scans and digital substraction angiography established the diagnosis.
Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1
Authors: Sone S , Yanagawa H , Nishioka Y , Orino E , Bhaskaran G , Nii A , Mizuno K , Heike Y , Ogushi F , Ogura T
Published: November 2022

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.
Pleuropulmonary changes during treatment of Parkinson's disease with a long-acting ergot derivative, cabergoline
Authors: Frans E , Dom R , Demedts M
Published: November 2022

A patient with Parkinson's disease, initially treated with bromocriptine and subsequently with cabergoline, developed progressive pleuropulmonary abnormalities during the latter therapy. These lesions even worsened for some weeks after interruption of cabergoline, which may possibly be related to the prolonged action of this drug. Thus cabergoline may cause similar pleuropulmonary abnormalities to bromocriptine.
The risk of lung cancer and mesothelioma after cessation of asbestos exposure: a prospective cohort study of shipyard workers
Authors: Sanden A , Jarvholm B , Larsson S , Thiringer G
Published: November 2022

A prospective cohort study of 3,893 shipyard workers, mainly exposed to chrysotile, indicated no increased risk of lung cancer 7-15 yrs after exposure to asbestos had ceased. The shipyard workers, however, had an increased risk of pleural mesotheliomas with 11 observed cases versus 1.5 expected. An explanation for these observations may be that asbestos may have different carcinogenic mechanisms in causing lung cancer and mesothelioma. A non-increased risk of lung cancer some years after exposure to asbestos has stopped is in accordance with asbestos acting as a promotor. The high risk of mesothelioma, on the other hand, may indicate that asbestos acts as a complete carcinogen in developing this disease.
Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment
Authors: Moser KM , Auger WR , Fedullo PF , Jamieson SW
Published: November 2022

Chronic, major vessel thromboembolic pulmonary hypertension (CTEPH), is an uncommon condition which, in the past, was an autopsy curiosity. Advances in diagnostic approaches, surgical techniques and postoperative management have transformed this disorder into a potentially curable form of pulmonary hypertension. The predominant symptom is unexplained dyspnoea on exertion. In patients with this complaint, CTEPH should be considered. Numerous pitfalls exist along the diagnostic path. Perfusion lung scans point toward the diagnosis, but often underestimate the extent of central arterial obstruction. Pulmonary angiography is the key diagnostic procedure, but the many patterns of thrombus organization-recanalization require a base of experience for proper interpretation. Criteria for selection of patients for surgery are evolving, but assurance of thrombus accessibility to surgery is critical. Surgical thromboendarterectomy bears no resemblance to acute pulmonary embolectomy. Recognition of thrombus (versus normal intima), meticulous dissection and a bloodless surgical field are essential for adequate restoration of pulmonary vascular patency. Multiple complications may arise postoperatively, and detailed attention to these is required for patient survival. With a co-ordinated, multi-specialty team effort, however, haemodynamic and clinical outcomes have been rewarding and persist long-term. Surgical mortality should steadily decline with such a co-ordinated effort, as well as earlier diagnosis and advances in surgical and postoperative management techniques.
Cytomegalovirus (CMV) pneumonitis in AIDS patients: the result of intensive CMV replication?
Authors: Aukrust P , Farstad IN , Froland SS , Holter E
Published: November 2022

We report a case of fatal pulmonary disease in a patient infected with human immunodeficiency virus (HIV), where cytomegalovirus (CMV) was the only causative agent identified in the lungs at autopsy. The most prominent histopathological features were numerous interalveolar cells containing CMV inclusion bodies combined with scanty signs of inflammation. We propose that the lung damage caused by CMV in acquired immune deficiency syndrome (AIDS) patients is a direct consequence of cytopathogenic effects of the virus related to the extent of active virus replication.
High prevalence of asthma in patients with bronchiectasis in Hong Kong
Authors: Ip MS , So SY , Lam WK , Yam L , Liong E
Published: November 2022

Eighty five Chinese patients with diffuse or localized bronchiectasis (non-cystic fibrosis) were studied regarding the prevalence of asthma. Twenty three of the 85 had concomitant asthma, diagnosed by history and reversibility on lung function testing either spontaneously or after bronchodilator. None fulfilled the diagnostic criteria of allergic bronchopulmonary aspergillosis (ABPA). Asthma preceded the onset of bronchiectasis in 13 patients and developed after long duration of bronchiectasis in seven, while the temporal onset could not be differentiated in three patients. Patients with both asthma and bronchiectasis had inferior spirometric values, higher prevalence of bronchial hyperresponsiveness to methacholine, higher prevalence of skin atopy, elevated serum immunoglobulin E (IgE), and more sputum eosinophilia, compared with their non-asthmatic counterparts. Possible mechanisms by which asthma and bronchiectasis predispose to each other include asthmatic obstruction contributing to development of bronchiectasis, and sensitization of airways with increased lability due to microbial colonization of the ectatic bronchial tree.
Role of the physiochemical properties of mucus in the protection of the respiratory epithelium
Authors: Girod S , Zahm JM , Plotkowski C , Beck G , Puchelle E
Published: November 2022

The respiratory mucus is a very complex biological material, which possesses both flow and deformation rheological properties, characterized by non-linear and time-dependent viscoelasticity and physical properties of adhesiveness and wettability. Viscosity and elasticity are directly involved in the transport capacity of mucus, whereas wettability and adhesiveness contribute to the optimal interface properties between the mucus and the epithelial surface. Optimal conditions for the protective and lubricant properties of respiratory mucus are represented by high wettability, and adhesiveness high enough not to induce flow of mucus in the respiratory bronchioles under gravity but low enough to mobilize mucus by airflow during coughing. An intermediate viscoelasticity is also required for an optimal mucociliary transport. Different biochemical constituents such as glycoproteins, proteins, proteoglycans and lipids are involved in the gel properties of respiratory mucus. During bronchial infection and particularly in cystic fibrosis, the loss of water and the increase in macromolecules result in a marked increase in viscosity and adhesiveness responsible for the mucus transport impairment. The various lipids present in mucus contribute differently to the physicochemical properties. Surface-active phospholipids, such as phosphatidylcholine and phosphatidylglycerol improve the wettability of mucus, whereas neutral lipids and glycosphyngolipids contribute to the hyperviscosity of mucus during infection. Phospholipids and associated mucins are also implicated in the interaction between bacteria and epithelial cells. Therefore, the respiratory mucus needs appropriate physicochemical properties for the protection, hydration and lubrication of the underlying airway epithelium.
Changes of nebulizer output over the years
Authors: Merkus PJ , van Essen-Zandvliet EE , Parlevliet E , Borsboom G , Sterk PJ , Kerrebijn KF , Quanjer PH
Published: November 2022

The effects of long-term use and of cleaning on the output of 30 specimens of DeVilbiss 646 nebulizers were investigated in order to assess their influence on outcome and interpretation of inhalation provocation tests. Output was assessed in a standardized manner based on weight loss on four occasions one year apart. Output was highly reproducible (intraclass correlation greater than or equal to 0.90), and varied considerably between nebulizers, necessitating calibration at least once. Inadequate cleaning diminished nebulizer output by a factor of two (p less than 0.01), while long-term use was associated with a moderate increase in output of 0.28 mg.yr-1 (p less than 0.0001). Bronchial responsiveness can be underestimated by about one doubling dose due to inadequate cleaning, while interchanging nebulizers can lead to overestimation or underestimation by up to one doubling dose. With proper care the increase in output due to wear has no consequences for clinical practice, or for longitudinal studies.
Alveolar macrophage populations are distorted in immunocompromised patients with pneumonitis
Authors: Bray DH , Squire SB , Bagdades E , Mulvenna PM , Johnson MA , Poulter LW
Published: November 2022

Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)-infected individuals and 12 transplant recipients. Nine normal volunteers acted as controls. The cells were washed and cytospins prepared. Monoclonal antibodies (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA-DR molecules as well as phenotypic macrophage markers. P values apply to the differences between medians using the Mann-Whitney test. Median percentages of macrophages, lymphocytes and neutrophils were similar in all three groups. No differences were found in the median percentages of macrophages expressing the monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and transplant recipients a median of only 45% of macrophages expressed the pan-macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the normal volunteers. The AM population expressing the dendritic cell marker (MoAb RFD1) was also markedly reduced in both groups of immunocompromised patients (2 vs 28% in normal volunteers). Transplant recipients had significantly more phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs 2%), but the numbers were still low when compared with the volunteers (48%). HLA-DR expression on BAL cells was reduced by 90% in both immunocompromised groups. For the transplant recipients, severity of pneumonitis was correlated with expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538, p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05), while no such correlation was found in HIV-infected patients. These results suggest that a defective macrophage population is probably a serious factor contributing to immunosuppression.
Time trends in repeated spirometry in children
Authors: Hoek G , Brunekreef B
Published: November 2022

In a study on acute health effects of air pollution in the Netherlands, pulmonary function has been measured repeatedly in children aged 7-11 yrs. In study periods of approximately 3 months, 6-10 tests have been made in a group of 1,621 children. The spirometric data have been examined for the presence of trends of pulmonary function with day of study, independent of air pollution. Peak expiratory flow (PEF) increased more than expected from normal lung growth, whereas for maximal mid-expiratory flow (MMEF) a decrease with time was observed. For forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) a smaller than expected increase with time was observed. The observed deviation from the expected pattern was larger for the children with a one week interval between successive tests than for the children with a three week interval. For FVC and FEV1 a non-linear relationship with time was observed, for PEF and MMEF this relationship was approximately linear. The particular changes of spirometric variables with time need to be taken into account when repeated lung function tests are performed to investigate acute effects of air pollution exposure.
Lung function impairment following mycoplasmal and other acute pneumonias
Authors: Laitinen LA , Miettinen AK , Kuosma E , Huhtala L , Lehtomaki K
Published: November 2022

We prospectively studied the lung function of 106 consecutive young patients with pneumonia. At the time of hospital admission we observed impaired spirometric function in 48% of the patients. During and following treatment, the frequency of abnormalities in pulmonary function tests decreased rapidly. However, at the 15th day of hospitalization, abnormal ventilatory function was still demonstrated in 21% of the patients. Such prolonged impairment of ventilatory function was significantly more likely to result from pneumonia caused by Mycoplasma pneumoniae than from forms caused by adenovirus or Streptococcus pneumoniae.
Repeated inhalation of bradykinin attenuates adenosine 5'-monophosphate (AMP) induced bronchoconstriction in asthmatic airways
Authors: Polosa R , Rajakulasingam K , Church MK , Holgate ST
Published: November 2022

Repeated bronchial challenges with inhaled bradykinin lead to a rapid loss of the bronchoconstrictor response and this has been suggested to be due to depletion of contractile neuropeptides from sensory nerve endings. If adenosine 5'-monophosphate (AMP), another potent bronchoprovocant in asthma, and bradykinin share a common pathway in inducing bronchoconstriction in asthmatic subjects, then repeated bradykinin bronchoprovocation tests should reduce the response to subsequent inhalation of AMP. We examined this hypothesis in eight asthmatic subjects in a double-blind, randomized study. On the histamine study day, two consecutive concentration-response studies with inhaled histamine were followed by a third consecutive challenge with AMP and the provocation concentration producing a 20% fall in forced expiratory volume in one second from the post-diluent baseline value (PC20 FEV1) for this agonist was calculated. On the bradykinin study day, two consecutive bronchoprovocation tests with bradykinin were followed by a third inhalation challenge to obtain the PC20AMP value. On a further occasion, the asthmatic subjects underwent two consecutive concentration-response studies with inhaled bradykinin followed by a third consecutive challenge with histamine. On the histamine study day, the geometric mean PC20AMP value was 28.1 mg.ml-1, whilst on the bradykinin study day, the fifteenfold reduction in bradykinin responsiveness after the second bradykinin challenge was accompanied by a significant reduction of the airway responsiveness to AMP, the PC20AMP being 59.8 mg.ml-1. A similar reduction in bradykinin responsiveness failed to alter the airway response to a subsequent inhalation with histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Growth factor activity in the lung during compensatory growth after pneumonectomy: evidence of a role for IGF-1
Authors: McAnulty RJ , Guerreiro D , Cambrey AD , Laurent GJ
Published: November 2022

Unilateral pneumonectomy in rats causes compensatory growth of the remaining lung. During this growth, there are large increases in the cell numbers and in the rates of collagen and non-collagen protein production. We examined possible mechanisms by which these changes might occur. Assessment of the effect of bronchoalveolar lavage (BAL) fluid on fibroblasts in vitro demonstrated the presence of stimulatory activity for fibroblast replication in control animals. This activity was greatly increased two and six days postpneumonectomy (115 +/- 26% and 75 +/- 18% above control values, respectively), but had returned to normal by 14 days. Preliminary characterization suggests that the activity is heat labile and consists of at least two moieties with apparent molecular weights of 5-15 kD and 70-220 kD. The activity was partially blocked by antibodies to insulin-like growth factor-1 (IGF-1), and levels of IGF-1 were increased by about 100% (p less than 0.001) two days after pneumonectomy compared with control values. Examination of BAL cells demonstrated an early influx of leucocytes into the remaining lung of pneumonectomized rats. At two days, about 25% of the lavageable cells were neutrophils, but macrophages were the predominant cell type at all times. The extravascular albumin space of the lung increased by about 65% (p less than 0.01), six days after pneumonectomy. The influx of circulatory proteins and cells are potential sources of the increased mitogenic activity observed in the lung.
Bronchiolitis obliterans organizing pneumonia (BOOP): the cytological and immunocytological profile of bronchoalveolar lavage
Authors: Costabel U , Teschler H , Guzman J
Published: November 2022

The cytological and immunocytological profile of bronchoalveolar lavage (BAL) was studied in 10 patients with idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) and compared with the data in idiopathic pulmonary fibrosis (IPF) (n = 22), chronic eosinophilic pneumonia (CEP) (n = 9), and extrinsic allergic alveolitis (EAA) (n = 24). Lymphocyte subsets were enumerated using an immunoperoxidase slide assay. The BAL pattern in BOOP patients was characterized by several features: 1) colorful cell differentials with an increase in all cell types, most markedly in lymphocytes, and more moderately in neutrophils, eosinophils and mast cells, as well as the presence of foamy macrophages and, occasionally, of plasma cells; 2) decreased CD4/CD8 ratio; 3) normal percentage of CD57+ cells; and 4) increase in activated T-cells in terms of human leucocyte antigen-DR (HLA-DR) expression, and occasionally also interleukin-2 receptor (CD25) expression. The findings were most similar to those in EAA except for the CD25 expression, which was always normal, and the CD57+ cells, which were increased in EAA. The increase in lymphocytes discriminated best between BOOP and IPF. The eosinophils were significantly higher in CEP than in BOOP with little overlap. In conclusion, BAL may be of value to distinguish between BOOP and other interstitial lung disease.