bluuebunny/crossref_metadata_2025 huggingface dataset:
Amiodarone toxicity: recurrence of interstitial pneumonitis after withdrawal of the drug
Authors: Parra O , Ruiz J , Ojanguren I , Navas JJ , Morera J
Published: November 2022

Amiodarone hydrochloride, an iodinated benzofuran derivative, is effective for treatment of supraventricular and ventricular arrhythmias. Pulmonary fibrosis has been reported after treatment with this drug. We present a patient with amiodarone pulmonary toxicity, who initially responded to corticosteroid therapy, but who developed a clinical relapse two months after withdrawal of the drug.
No effect of oral high frequency oscillation combined with forced expiration manoeuvres on tracheobronchial clearance in chronic bronchitis
Authors: van Hengstum M , Festen J , Beurskens C , Hankel M , van den Broek W , Corstens F
Published: November 2022

This study compared the effect of oral high frequency oscillation (OHFO) with the effect of the forced expiration technique (FET) on tracheobronchial clearance. Eight patients with chronic bronchitis were investigated (mean age 60 +/- 10 yrs, mean forced expiratory volume in one second (FEV1) 68 +/- 27% predicted, mean sputum production 33 +/- 9 g.day-1). OHFO was applied at the respiratory system resonant frequency of each patient (range 9.2-25 Hz) and combined with huffing. FET included breathing exercises, huffing and postural drainage. Duration of both OHFO and FET was 30 minutes. Tracheobronchial clearance was measured by means of a radio-aerosol technique. At 60 mins after start of the treatment mean tracheobronchial retention was 70 +/- 26% after OHFO, 54 +/- 26% after FET and 76 +/- 18% in the control run, which included huffing only. OHFO was not significantly different from control. FET was significantly different (p less than 0.02) from both OHFO and control. It is concluded that OHFO has no effect on tracheobronchial clearance in chronic bronchitis.
The action of platelet activating factor and its antagonism by WEB 2086 on human isolated airways
Authors: Johnson PR , Armour CL , Black JL
Published: November 2022

This study investigated the direct and indirect effects of platelet activating factor (PAF, PAF-acether) on human isolated airways. PAF caused a single non-repeatable contraction which was found to be variable both between lung samples and within tissues from the same lung. The range of contractions induced by PAF, 7 X 10(-8), M and 7 X 10(-7) M was 2-55% and 3-72% of the maximal response to carbachol, respectively. The PAF antagonist WEB 2086, 10(-6) M, inhibited the contraction induced by PAF, 7 X 10(-7) M, (p less than 0.05, n = 5). PAF caused a significant potentiation of the contractile effects of bolus doses of histamine. This potentiation was inhibited by WEB 2086, 10(-6) M, (p less than 0.05, n = 5). These results suggest firstly that the bronchoconstriction observed in man after PAF administration could be the result of an action of PAF on the smooth muscle or result from the action of a second mediator released by PAF from cells within the lung. Secondly, the bronchial hyperresponsiveness observed after PAF administration could be due to a specific alteration in smooth muscle sensitivity. The fact that WEB 2086 inhibited the contractile response to PAF and the potentiation of histamine-induced contraction would suggest that PAF receptors mediate these responses.
Relationship between airway obstruction, desaturation during exercise and nocturnal hypoxaemia in cystic fibrosis patients
Authors: Versteegh FG , Bogaard JM , Raatgever JW , Stam H , Neijens HJ , Kerrebijn KF
Published: November 2022

We measured pulmonary function, responses to exercise and oxygen saturation (So2) at rest, and also before and during sleep in 24 patients with cystic fibrosis in a varying degree of severity. The pulmonary function indices analysed were forced expiratory volume in one second (FEV1), total lung capacity (TLC), measured by body plethysmography (TLC box) and Helium dilution (TLC He), residual volume measured by body plethysmography (RV) and the amount of trapped air (TA = TLC box-TLC He). The exercise variables included symptom limited maximal oxygen uptake (Vo2max), maximum minute ventilation (VEmax) and So2, at rest in sitting position and during maximal exercise. So2 was measured by ear oximetry. The lowest mean So2 obtained in two consecutive nights over a period of 1 hour was taken as the indicator of nocturnal oxygen saturation. A high correlation existed between resting supine and sitting So2, and the degree of nocturnal hypoxaemia (0.84 and 0.76, respectively). Highly significant correlations existed also for the indices of airway obstruction, Vo2 max and lowest So2 at exercise versus the nocturnal lowest hourly mean So2. From all variables a resting So2 in the sitting position lower than 94% appeared to be most predictive of nocturnal desaturation and indicates a risk of nocturnal hypoxaemia in patients with cystic fibrosis.
Bronchial responsiveness in patients with mitral valve disease
Authors: Rolla G , Bucca C , Caria E , Scappaticci E , Baldi S
Published: November 2022

Bronchial responsiveness has been evaluated in patients with chronic lung congestion secondary to mitral valve disease. Methacholine bronchial challenge was performed by intermittent aerosol generation in 31 patients with mitral valve disease, 18 in New York Heart Association (NYHA) Class II and 13 in NYHA Class III, non-atopic and with baseline forced expiratory volume in one second/vital capacity (FEV1/VC) greater than 85% of predicted and in 30 normal controls. Haemodynamic data were available in 17 patients. The methacholine bronchial provocation dose causing a 35% fall of airway conductance (PD35sGaw) was significantly lower in patients (507 +/- C.I. 205 micrograms) than in normals (2779 +/- C.I. 358 micrograms), (p less than 0.001). In patients log PD35sGaw was significantly correlated with mean pulmonary artery pressure (r = 0.53, p less than 0.05), mean pulmonary capillary wedge pressure (r = 0.67, p less than 0.01), but not with any spirometric parameters. Bronchial hyperresponsiveness seems to be common in patients with mitral valve disease and evidence of lung congestion.
Inhalational challenge using hypertonic saline in asthmatic subjects: a comparison with responses to hyperpnoea, methacholine and water
Authors: Smith CM , Anderson SD
Published: November 2022

Non-isotonic aerosols are being used increasingly for bronchial provocation testing in patients with asthma. We investigated changes in forced expiratory volume in one second (FEV1) in response to inhaling ultrasonically nebulized 4.5% saline in 10 normal subjects and 68 subjects with asthma. A comparison of the sensitivity to this challenge was made with sensitivity to challenge with methacholine, water, exercise and eucapnic voluntary hyperventilation (EVH). In normal subjects the FEV1 was reduced by 6 +/- 2% (mean +/- SD) after inhalation of 33 ml of aerosol. Eighty four percent of the asthmatic subjects exhibited a fall in FEV1 of greater than 20% after inhaling 4.5% saline. The provoking dose (geometric mean +/- 95% confidence limits) of saline to induce a 20% fall (PD20) was 2.05 ml (1.34-4.48). The sensitivity to inhaled 4.5% saline was significantly related (p less than 0.001) with responsiveness to methacholine, exercise and EVH, but not to water. Those patients recording a PD20 to 4.5% saline had a PD20 to methacholine less than 2 mumol which is a response consistent with moderate to severe bronchial hyperresponsiveness.
The hormonal response to exercise in asthma
Authors: Kallenbach JM , Panz V , Girson MS , Joffe BI , Seftel HC
Published: November 2022

The hormonal responses to exercise of 10 asthmatic patients and 12 normal subjects were compared by studying the changes in the plasma levels of growth hormone, prolactin, adrenocorticotropic hormone (ACTH) and cortisol induced by treadmill running. The asthmatic patients demonstrated absence of the plasma cortisol response to exercise (peak increment -15 +/- 21 (SEM) vs 108 +/- 34 nmol.l-1 p less than 0.02). None of these patients were being treated with systemic corticosteroids and there was no difference between the responses of users and non-users of beclomethasone dipropionate. The results suggest the presence of an impaired adrenocortical response to the stress of physical exercise in asthma and indicate the need for detailed evaluation of hypothalamic-pituitary-adrenal function in patients with the disease.
Efficacy of sustained release theophylline given at three different evening intake times in addition to a baseline medication
Authors: Siebert B , Kunkel G , Borner K , Staudinger HW , Steinijans VW
Published: November 2022

In this randomized crossover study of 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24 h pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement of 24 h peak expiratory flow values after adding theophylline to a drug therapy including inhalative beta 2-agonists and corticosteroids in nearly all and inhalative anticholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24 hr averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.
Human pulmonary infection with Corynebacterium equi
Authors: Egawa T , Hara H , Kawase I , Masuno T , Asari S , Sakurai M , Kishimoto S
Published: November 2022

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.
PEEP-masks in patients with severe obstructive pulmonary disease: a negative report
Authors: Christensen HR , Simonsen K , Lange P , Clementsen P , Kampmann JP , Viskum K , Heideby J , Koch U
Published: November 2022

Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.
Diabetes mellitus and ventilatory capacity: a five year follow-up study
Authors: Lange P , Groth S , Mortensen J , Appleyard M , Nyboe J , Schnohr P , Jensen G
Published: November 2022

During a five year observation period, declines of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were investigated in 200 subjects with diabetes mellitus (DM), 126 subjects who developed DM during that period and 9,051 nondiabetic subjects. After statistical adjustment for age, sex, height, and tobacco consumption we found that the subjects who developed DM during the observation period had the steepest declines of ventilatory function. Their annual declines of FVC (and FEV1) were on average 29 ml (and 25 ml) greater than the declines observed among the nondiabetic subjects. The subjects who had DM during the whole observation period experienced a decline of ventilatory function which was not significantly greater than the decline among the nondiabetic subjects. Our results suggest that DM, at its onset, is associated with a significantly accelerated decline of ventilatory function. If DM has been present for some years, its impact on the decline of ventilatory function is small.
Endotoxin-induced plasma exudation in guinea-pig airways in vivo and the effect of neutrophil depletion
Authors: Evans TW , Rogers DF , Belvisi MG , Rohde JA , Chung KF , Barnes PJ
Published: November 2022

The contribution of neutrophils to the action of endotoxin on plasma exudation in the airways of anaesthetized guinea-pigs was quantified by measuring the extravasation of Evans blue dye. Endotoxin (Salmonella enteritidis) caused a dose-dependent increase in microvascular leakage to Evans blue dye which was maximal after 25 min (p less than 0.05). The minimum dose tested that induced a significant rise in leakage was 1.5 mg.kg-1 for "central" intrapulmonary airways (ipa); 4.5 mg.kg-1 for trachea and main bronchi and 7.5 mg.kg-1 for nasal mucosa, larynx and "peripheral" ipa. Depletion of circulating neutrophil numbers by 97% using an antibody to guinea-pig neutrophils caused no significant diminution of the effects of endotoxin on leakage in any part of the airway. There was no significant influx of neutrophils into the airway interstitium at the time of maximum extravasation of Evans blue. We conclude that endotoxin-induced airway microvascular permeability is dependent upon mechanisms other than circulating neutrophils.
The role of increased airway microvascular permeability and plasma exudation in asthma
Authors: Chung KF , Rogers DF , Barnes PJ , Evans TW
Published: November 2022

Airway oedema and inflammation are recognized as cardinal features of asthma, resulting from increase microvascular permeability of the bronchial circulation with the exudation of plasma and inflammatory cells into the airway lumen. Resistance to airflow is increased and the epithelium is disrupted either directly or by cytotoxic proteins derived from migrating inflammatory cells. Such mediators include bradykinin, platelet-activating factor (PAF), leukotrienes and histamine. Antigen-induced and neurogenic inflammation, generated by immunoglobulin E (IgE) and neuropeptides respectively, may also contribute to oedema generation. Assessment of increased bronchial vascular permeability in animals has largely involved measurement of the extravasation of radiolabelled albumin or protein-bound dyes. Non-invasive techniques are less reliable in humans, but measurement of the rate of clearance of inhaled particles labelled with isotope may prove successful. Airway oedema appears to be an important feature of asthma and future research may be aimed at developing drugs that specifically prevent airway microvascular leakage.
Dry air-induced late phase responses in the canine lung periphery
Authors: Freed AN , Adkinson NF
Published: November 2022

Although controversial, late phase responses in asthmatic subjects have been reported several hours after exercise. We previously showed that exposure to dry air increases collateral system resistance (Rcs) in the canine lung periphery, and produces acute airway responses analogous to those that characterize human exercise-induced asthma. We used a dual wedged bronchoscope technique in anaesthetized male mongrel dogs to monitor Rcs in: 1) control segments continuously exposed to 200 ml.min-1 of 5% CO2 in air and 2) dry air challenged segments exposed to 2000 ml.min-1 5% CO2 for 5 min. We examined Rcs at 5 min and approximately 5 h post-challenge in an attempt to document late phase airway obstruction. Five min after dry air challenge Rcs initially increased 114 +/- SE 22%; contralateral control segments remained unchanged (n = 9). Five hour post-challenge, Rcs in dry air exposed segments was elevated 81 +/- 20% above pre-challenge baseline (p less than 0.01); contralateral control segments did not change significantly over the 5 h period. Cell profile analyses of lavage samples at 5 hours revealed that neutrophils and eosinophils were significantly increased (p less than 0.03) in dry air challenged segments when compared to controls. Leukotriene C4/D4 concentration in lavage was correlated (p less than 0.02) with neutrophil infiltration. Thus, we conclude that the canine lung periphery represents a reproducible model of a dry air-induced late phase reaction.
Familial elevation of serum angiotensin converting enzyme activity
Authors: Luisetti M , Martinetti M , Cuccia M , Dugoujon JM , De Rose V , Peona V , Pozzi E , Grassi C
Published: November 2022

A clustering of high levels of serum angiotensin converting enzyme (S-ACE) was found in an Italian family. The elevation affected five subjects, two of whom were completely healthy and free from known causes of S-ACE increase. The values of S-ACE in hyperACEmic subjects exceeded the values found in normal relatives severalfold. HyperACEmia seemed to be inherited as an autosomal dominant trait. Immunogenetic studies were performed, but we did not find a genetic marker for this condition. The S-ACE activity was inhibited in vitro by edetic acid (EDTA) and SQ 14,225 (captopril). The S-ACE activity was also determined after 1:8 dilution and dialysis against saline of sera. From these experiments we deduced that Lieberman's intrinsic ACE inhibitor was lacking in the hyperACEmic sera. In the presence of remarkable S-ACE increase, a congenital elevation of S-ACE should be considered and it would be useful to perform a familial investigation.
The tubular maximum for calcium reabsorption in patients with chronic active thoracic sarcoidosis
Authors: Broulik PD , Votava V , Pacovsky V
Published: November 2022

The tubular maximum for calcium reabsorption (TmCa) was evaluated in 52 patients with chronic active thoracic sarcoidosis. Hypercalcaemia was found in five patients (9.6%). The mean serum calcium value of 2.54 +/- 0.18 mmol.l-1 in patients with sarcoidosis was significantly higher than that obtained in the control group (2.42 +/- 0.11 mmol.l-1). The mean TmCa in patients with sarcoidosis (2.11 +/- 0.26 mmol.l-1 glomerular filtrate (GF] was not statistically different from the mean TmCa for the group of healthy subjects (2.18 +/- 0.23 mmol.l-1 GF). Urinary sodium corrected TmCa in both groups of patients was affected in a similar way. Our study demonstrates for the first time that there is no increase in TmCa in patients with chronic active thoracic sarcoidosis. Hypercalcaemia is not a result of an increased TmCa.
Effect of aminophylline and verapamil upon diaphragmatic force generation in dogs
Authors: De Vito EL , Roncoroni AJ
Published: November 2022

The effects on the diaphragm of verapamil (VPM) and aminophylline (AMP) were studied in dogs during stimulation of phrenic nerves at the 5th cervical roots (5th-PS) or transvenously at the trunk (T-PS). Transdiaphragmatic pressure (Pdi)/frequency curves were constructed. Our findings were: 1) AMP increased Pdi at all stimulation frequencies (p less than 0.01) during 5th-PS but only at 10-30 Hz during T-PS; 2) in other dogs infusion of VPM (0.14 mg.kg-1.min-1) decreased Pdi at all frequencies (p less than 0.025) without change in diaphragmatic blood flow; 3) the effects of VPM were completely reverted by AMP; 4) after a large amount of AMP, infusion of VPM (0.21 mg.kg-1.min-1) decreased Pdi at all frequencies. Since these drugs have several mechanisms of action and do not show mutual blocking effect, different action sites are suggested.
Domiciliary nebulized terbutaline in severe chronic airways obstruction
Authors: Hansen NC , May O
Published: November 2022

Forty-eight patients with severe chronic airways obstruction were given 5 mg terbutaline or placebo from a nebulizer twice daily for 2 + 2 weeks. Twenty three patients preferred terbutaline, 9 placebo and 16 had no preference. The baseline lung function and the 6 minute walking distance were not increased after the terbutaline period. The patients who preferred terbutaline indicated less dyspnoea after the terbutaline period as compared to the placebo period, but did not differ with regard to lung function or walking distance after the terbutaline treatment. The physiology behind the subjective relief from the terbutaline inhalations remains unexplained.
Spontaneous pneumothorax following regression of pulmonary metastases
Authors: Kryger-Baggesen N
Published: November 2022

Spontaneous pneumothorax (SP) caused by necrosis in combination with regression of lung metastases is a rare complication to cancer chemotherapy. Few case reports have previously been presented, and mostly in patients with sarcomas. A patient is presented with spontaneous pneumothorax probably caused by chemotherapy-induced cell necrosis in bilateral lung metastases secondary to an endometrioid cancer. The literature is surveyed. Because of the increasing use of effective chemotherapeutic drugs, it is expected that this rare complication will occur more often.
Fibroblast-alveolar cell interactions in sarcoidosis and idiopathic pulmonary fibrosis: evidence for stimulatory and inhibitory cytokine production by alveolar cells
Authors: de Rochemonteix-Galve B , Dayer JM , Junod AF
Published: November 2022

To better understand how the activity of inflammatory cells collected by bronchoalveolar lavage (BAL) could affect the outcome of granulomatous and fibrotic pulmonary diseases, we studied secretory products and messenger ribonucleic acid (mRNA) expression for certain cytokines of BAL cells in 10 controls, 14 patients with interstitial pulmonary fibrosis (IPF) and 22 patients with sarcoidosis. We assayed the activity of 48 h conditioned media for: 1) their biological action on fibroblast proliferation and prostaglandin E2 (PGE2), collagenase and collagen production by fibroblasts; 2) TNF alpha levels by bioassay and radioimmunoassay; 3) interleukin 1 (IL-1) alpha and beta and beta levels by solid phase enzyme immunoassay (EIA); 4) tumor necrosis factor (TNF) and IL-1 inhibitory activity. We also measured, in freshly isolated BAL cells: 1) mRNA levels for IL-1 alpha and beta and TNF alpha; 2) cell-associated IL-1 alpha and beta by EIA. The only difference found in the assessment of the biological activity of BAL cells conditioned medium was an increase in fibroblast proliferation in sarcoidosis vs IPF patients. The IL-1 alpha and beta, and TNF alpha contents of conditioned media were similar in the three groups. Inhibitory activity against IL-1 and TNF alpha was found in a few patients. Further analysis revealed two peaks of inhibitory activity against IL-1 (20-25 kD and 35-40 kD), as well as a distinct TNF alpha inhibitory activity which could be retained on a TNF alpha-binding affinity column. No mRNA expression for TNF alpha was found in freshly isolated BAL cells, whereas very variable levels of IL-1 alpha and beta mRNA levels were detected in the three groups. Because of these variable results of differences in functional state between freshly isolated and cultured BAL cells, and of the presence of inhibitory substances against IL-1 and TNF alpha, it is unlikely that the development of fibrosis could be ascribed to a single disorder or abnormality.
Intrapulmonary distribution of 99mtechnetium labelled ultrafine carbon aerosol (Technegas) in severe airflow obstruction
Authors: Crawford AB , Davison A , Amis TC , Engel LA
Published: November 2022

Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTechnetium (99mTc), has been recently introduced for clinical imaging of lung ventilation. In 12 selected subjects with severe chronic airflow limitation (FEV1 = 0.89 +/- 0.22; mean +/- SD, l) we have studied the regional intrapulmonary distribution of TG and compared it quantitatively with that of 133Xenon (133Xe). A 133Xe equilibration image was acquired for 10-15 s during a breathhold at total lung capacity (TLC). Six subjects (Group 1) inspired 100 ml boli of TG or 133Xe from functional residual capacity (FRC) and another 6 subjects (Group 2) inspired 1.0 l of labelled gas from FRC followed by air to TLC at a constant flow rate less than 0.5 l.s-1. Lung images were then acquired with the chest position rigorously controlled. From the equilibration image, upper, middle, lower, central and peripheral regions were defined. Relative regional fractional concentrations (RFC) were then calculated using the equilibration image to correct for ventilated lung volume. In addition, in four of the Group 2 subjects, each lung image was divided into multiple regions (12-17 per lung). The RFC were then calculated as above (RFCM). The highest and lowest RFC were not significantly different between 133Xe and TG in either Group 1 or Group 2 subjects. Similarly the RFCM analysis showed no systematic difference between 133Xe and TG. The ratio of peripheral to central RFC constitutes a penetration index which for TG was 0.99 +/- 0.23 that of 133Xe. Our results indicate that even in the presence of severe airflow limitation the radiolabelled tracer TG mimics the regional distribution of a real gas.
Biology of small cell lung cancer: an overview
Authors: Weynants P , Humblet Y , Canon JL , Symann M
Published: November 2022

Despite disappointing results in the treatment of small cell lung cancer (SCLC), major progress in our understanding of SCLC biology has occurred in the past decade. Advances in the technique for culturing SCLC tumours in vitro have greatly facilitated the study of the biological properties of this tumour. The major progress in our understanding of SCLC includes: 1) the availability of nonspecific biological tumour markers such as neuron-specific enolase (NSE), the BB isoenzyme of creatine phosphokinase (CPKBB), bombesin/gastrin releasing peptide (GRP) and chromogranin A; 2) the generation of monoclonal antibodies raised against the neural and epithelial features of SCLC tumours; 3) the identification of several autocrine growth factors such as bombesin/GRP, insulin-like growth factor (IGF), transferrin and physalaemin; 4) the close study of cytogenetic abnormalities leading to the discovery of a unique chromosomal deletion of the short arm of chromosome 3 (del 3p 14-21), and to changes in oncogenic expression, e.g. c-myc, L-myc and N-myc, accounting for known biological and treatment results. These data suggest that all lung cancers arise from a common stem cell of endodermal origin. The information derived from these biological studies represents the most promising avenue towards new treatment strategies in SCLC.
Pharmacokinetics of antibiotics in the lungs
Authors: Valcke Y , Pauwels R , Van der Straeten M
Published: November 2022

This paper reviews current knowledge on the relationship between local penetration or antibiotics and therapeutic efficacy in pulmonary and bronchial infections. The antimicrobial drug concentration at the site of infection is supposedly determinative for the efficacy of the antibiotic treatment but the number of studies in respiratory infections supporting this hypothesis is limited. The mechanisms responsible for the pulmonary deposition or orally or systemically administered antibiotics include passive diffusion, active transport, bulk flow and permeation. The penetration of antimicrobial drugs into the respiratory tract is influenced by both host-related factors, such as inflammation or mechanical injury, and drug-related factors, such as molecular weight. In addition, local bio-inactivation can occur. The final bioactive antibiotic concentration at the site of the respiratory infection is, therefore, the result or a very complex dynamic process. Different sampling and measuring methods have been used for the assessment of antibiotic concentrations at the site of respiratory infections. Concentrations in sputum, bronchial secretions and biopsy specimens have been correlated with serum concentrations and clinical outcome. Bronchoalveolar lavage could be a promising technique for evaluating antibiotic drug concentrations in alveolar lining fluid. For many antibiotics, data concerning penetration and pharmacokinetic behaviour in the respiratory tract are lacking.
Aetiology, outcome and prognostic factors in community-acquired pneumonia requiring hospitalization
Authors: Ortqvist A , Hedlund J , Grillner L , Jalonen E , Kallings I , Leinonen M , Kalin M
Published: November 2022

Outcome and prognostic factors were prospectively studied in 277 adult patients (average age 62 yrs) with community-acquired pneumonia requiring hospitalization. The aetiology was established in 68%, with S. pneumoniae as the predominating agent. Mortality was 4% (12 of 277), and all but one who died were greater than or equal to 60 yrs of age. Features associated with high mortality included greater age, absence of chills and chest pain, high respiratory rate (greater than 30 breaths.min-1) and low serum albumin on admission, and the occurrence of airway colonization and secondary infection during hospital stay. Multivariate analysis showed that low serum albumin and the occurrence of secondary infection, but also absence of chills and airway colonization, were correlated to a higher mortality. In patients who survived, the median length of hospital stay was seven days, and at follow-up, about eight weeks after admission, 81% had recovered and chest X-ray was normal in 84%. In conclusion, we believe that the outcome of community-acquired pneumonia can be influenced by prophylactic measures against pneumococcal infection, and an increased surveillance of risk patients.
High amylase activity in pleural fluid and primary bronchogenic adenocarcinoma
Authors: Devuyst O , Lambert M , Scheiff JM , Francart J
Published: November 2022

We report a case of primary bronchogenic adenocarcinoma, complicated by pleural effusion, in which very high pleural amylase activity was found, whilst serum amylase was normal. Isoamylase determination showed a salivary-type amylase. Concerning the origin of this enzyme, ultrastructural study of the malignant cells obtained from the pleural fluid suggested a local amylase synthesis. The pathophysiological significance of electron-dense granules found in these cells is also discussed.
Chest physiotherapy in hospitalized patients with cystic fibrosis: a study of lung function effects and sputum production
Authors: Oberwaldner B , Theissl B , Rucker A , Zach MS
Published: November 2022

In order to evaluate the short-term lung function effects of high-pressure positive expiratory pressure (PEP)-mask physiotherapy (PT) in relation to PT-assisted sputum production, we studied 18 patients with cystic fibrosis (CF), hospitalized for a pulmonary exacerbation. Lung functions were measured before (a) and after PT (b) on day one (1), five (2), ten (3) and fifteen (4). Five functions improved significantly from a1 to b1, eight from a2 to b2, seven from a3 to b3, and seven from a4 to b4. Baseline (a) measurements improved only slightly, but post-PT (b) values improved more markedly from 1 to 4, and this improvement reached statistical significance for six functions; consequently, a-to-b lung function changes tended to increase from investigation 1 to 4. Eleven PT-induced lung function changes correlated to the weight of sputum produced. High-pressure PEP-mask PT therefore resulted in significant lung function improvements, and not only maintained but increased its effect in the course of the hospitalization.
Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight
Authors: Watts JL , Milner R , Zipursky A , Paes B , Ling E , Gill G , Fletcher B , Rand C
Published: November 2022

In a randomized trial to determine whether oral vitamin E reduced stages III and IV bronchopulmonary dysplasia (BPD) by 50%, 268 infants were randomly allocated, after stratification by birth weight and severity of disease, to receive vitamin E 25 units or an indistinguishable placebo. The experimental (E) group and the control (C) group were similar in weight, gestational ages, Apgar scores, severity of illness, and initial oxygen and ventilator exposure. Serum vitamin E levels were significantly different within 48 h of administration and remained well above normal adult levels from the first week of life in the experimental group. There was no difference in the rates of early death, BPD at 28 days, or mortality from BPD. Severity was similar and no difference was seen in the incidence of necrotizing enterocolitis or sepsis. There was no evidence that vitamin E supplementation offered protection against chronic lung disease in infants less than 1,500 g birth weight.
Obstructive lung disease in northern Sweden: respiratory symptoms assessed in a postal survey
Authors: Lundback B , Nystrom L , Rosenhall L , Stjernberg N
Published: November 2022

The prevalence of respiratory symptoms in 6,610 adults (3,372 men and 3,238 women); 35-36, 50-51 and 65-66 yrs of age, living in selected areas of Norrbotten, northern Sweden, were assessed in a postal survey. Response rates were identical in men and women, and at least one respiratory symptom was reported by 41% of each sex. Twenty two percent reported sputum production, and 14% reported wheezing. Despite differences in smoking habits and in the different age groups, the prevalence of symptoms did not differ between the sexes, or between urban and rural areas. Symptoms were as common in people living in the rural interior as in the industrialized coastal area. Present or past history of asthma was reported by 323 (5.9%) subjects, whilst 234 (4.1%) subjects stated that they had chronic bronchitis or emphysema. Less than half of the subjects who reported attacks of breathlessness together with wheezing stated that they had at any time had asthma. Whilst the exact prevalence of had asthma. Whilst the exact prevalence of at any time had asthma and chronic bronchitis cannot be assessed from this postal survey, its results indicate that the prevalence of asthma may be higher in northern Sweden than has been reported from the south of Sweden.
Hyperosmolarity-induced increases in airway responsiveness and late asthmatic responses
Authors: Bussieres S , Turcotte H , Boulet LP
Published: November 2022

Airway responsiveness to inhaled methacholine was assessed before and after bronchial challenge with ultrasonically nebulized hyperosmolar saline (UNHS), and these changes were correlated with the development of late asthmatic responses (LAR). Sixteen subjects with mild to moderate asthma had two consecutive methacholine challenges before and one after a cumulative-dose challenge with UNHS. Twelve of these subjects also had a single-dose hyperosmolar challenge to document the occurrence of LAR and determine if UNHS had a significant cumulative-dose effect. If a LAR was observed, a control day without challenge completed the study. Responsiveness to methacholine was similar on the 2 baseline methacholine challenges with a provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) (mean +/- SEM) of 1.11 +/- 0.94 and 1.16 +/- 0.94 mg.ml.1 (r: 0.98). However, it was significantly increased after the inhalation of UNHS with a PC20 (mean +/- SEM) of 0.57 +/- 1.00 mg.ml.1 (p less than 0.001). Two subjects developed a late fall in forced expiratory volume in one second (FEV1) of 19 and 46% after hyperosmolar challenge. In this last subject, the LAR, not reproduced on the control day, was associated with a marked post-UNHS change in PC20, going from a baseline of 4.4 to 0.7 mg.ml.1 after UNHS. The % fall in FEV1 following the dose-response hyperosmolar challenge and the single-dose hyperosmolar challenge were not different, with mean values +/- SEM of 34.9 +/- 2.2 and 35.8 +/- 4.1, respectively, (p greater than 0.5). In conclusion, airway responsiveness to methacholine may increase following hyperosmolar saline inhalation, often unrelated to LAR.
Calculation of half-life of carcinoembryonic antigen after lung tumour resection: a case report
Authors: Verhelst J , Vanden Broecke E , Van Meerbeeck J , De Backer W , Blockx P , Vermeire P
Published: November 2022

Since little is known about carcinoembryonic antigen (CEA) half-life in humans, we followed changes in CEA levels after curative resection of a small bronchial adenocarcinoma in a 54 yr old man with an unusually high preoperative serum CEA level of 1,199 ng.ml-1. Serum CEA followed a four phase curve with an initial increase, attributed to release of CEA from the tumour, a rapid fall during four days (CEA half-life 3.2 days), a slower exponential decay to normal levels during almost three months (CEA half-life 11 days) and eventually maintenance of normal levels for 14 months. These results are consistent with data from animal experiments and a single report on CEA half-life in humans, but CEA half-life seems longer in man than in animals. This observation also suggests that a very high serum CEA level should not in itself preclude curative surgical resection of a primary bronchogenic carcinoma.
Pulmonary alveolar proteinosis: prolonged spontaneous remission in two patients
Authors: Martinez-Lopez MA , Gomez-Cerezo G , Villasante C , Molina F , Diaz S , Cobo J , Medrano C
Published: November 2022

Pulmonary alveolar proteinosis is a rare idiopathic diffuse airspace disease characterized by intra-alveolar accumulation of large quantities of lipoproteinaceous material, with preservation of the lung interstitium. The clinical course of pulmonary alveolar proteinosis is variable. Spontaneous resolution is known to occur in up to a quarter of the cases. We describe two patients with untreated pulmonary alveolar proteinosis who experienced complete clinical, functional and radiographic resolution. In follow-up periods of fourteen and six years, both patients have remained asymptomatic.
Mechanical load on the ventilatory muscles during an incremental cycle ergometer test
Authors: Wanke T , Formanek D , Schenz G , Popp W , Gatol H , Zwick H
Published: November 2022

An incremental cycle ergometer test performed with a total of 40 healthy subjects (25 male, 15 female) was used to study the mechanical load on the ventilatory muscles. The parameters for the mechanical load on the ventilatory muscles are the time integral of the oesophageal pressure and the mean oesophageal pressure change per time unit (dPoe/dTI) of each breathing manoeuvre. The pressure-time integral is the area delimited by the oesophageal pressure trace and the inspiratory time axis. It is expressed as a fraction of the product of the subject's maximum oesophageal pressure (Poe(max)) and total breath cycle duration (TTOT). This parameter is called oesophageal tension time index (TTIoe). The relationship between minute ventilation and these two parameters during ergometer test showed gender-specific variations because of the differences between men and women as to anthropometric data, lung function parameters and maximum ventilatory muscle strength. Moreover, the dPoe/dTI values significantly depend on the breathing frequency. The present study has provided evidence that, in general, the TTIoe and dPoe/dTI values in terms of a specific minute ventilation (VE) are higher in women than in men. Parameters for the mechanical load on the ventilatory muscles regarding the level of pressure to be generated as well as the duration and velocity of muscle contraction should therefore also allow for the gender of the patients.
The Dutch hypothesis (chronic non-specific lung disease) revisited
Authors: Sluiter HJ , Koeter GH , de Monchy JG , Postma DS , de Vries K , Orie NG
Published: November 2022

In 1961 the hypothesis (later referred to as the Dutch Hypothesis (DH)) was put forward that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors play a role in the pathogenesis. A hereditary predisposition to develop allergy and bronchial hyperreactivity were considered to be important denominators of disease susceptibility. Complications and complicating diseases would also contribute to the ultimate phenotype of the patient. In the present paper we discuss the relevance of this hypothesis in 1990. Until now it has not been refuted; circumstantial evidence in its favour has accumulated, but formal proof is still lacking. Further research should pay more attention to the genetic aspects of the disease. Arguments are presented against the use of the terms asthma, chronic bronchitis, and emphysema as indicators of disease entities, and in favour of the use of an umbrella-term, e.g. chronic non-specific lung disease (CNSLD), provided that, in addition, every patient is characterized using so-called defining criteria.
Adult respiratory distress syndrome (ARDS) due to bacteraemic pneumococcal pneumonia
Authors: Mannes GP , Boersma WG , Baur CH , Postmus PE
Published: November 2022

We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus pneumoniae is the most frequently found micro-organism responsible for community-acquired pneumonia. In 25-35% of these patients pneumococcal bacteraemia is found, with a 2-3 times higher mortality rate than that for non-bacteraemic pneumococcal pneumonia.
Effects of home environment on respiratory symptoms and lung function in a general population sample in north Italy
Authors: Viegi G , Paoletti P , Carrozzi L , Vellutini M , Ballerin L , Biavati P , Nardini G , Di Pede F , Sapigni T , Lebowitz MD , et al.
Published: November 2022

Effects of indoor pollution exposure were evaluated in a general population sample (n = 3,289) living in the Po River Delta area. Prevalence rates of chronic cough in men and dyspnoea in women were significantly higher in association with the use of bottled gas (propane) for cooking instead of natural gas (methane). Chronic cough and phlegm in men and dyspnoea in women were significantly associated with the use of a stove for heating. When combining type of heating and fuel used, in men a trend toward higher prevalence rates of chronic cough and phlegm was shown in those with stove or fan heating (regardless of the fuel); in women the trend reached statistical significance for dyspnoea. The relationship between stove (regardless of fuel) and decrease in forced expirograms was statistically significant only in women. In multiple logistic models, accounting for independent effects of age, smoking, pack-years, parents' smoking, socio-economic status, body mass index, significantly increased odds ratios were found in males for the associations of: bottled gas for cooking with cough (1.66) and dyspnoea (1.81); stove for heating with cough (1.44) and phlegm (1.39); stove fuelled by natural gas and fan or stove fuelled other than by natural gas with cough (1.54 and 1.66). In females, significantly increased odds ratios were found only for dyspnoea when associated with bottled gas for cooking (1.45), stove for heating (1.46), stove fuelled by natural gas (1.58), stove or fan fuelled other than by natural gas (1.73).(ABSTRACT TRUNCATED AT 250 WORDS)
A flow interruption device for measurement of airway resistance
Authors: Chowienczyk PJ , Lawson CP , Lane S , Johnson R , Wilson N , Silverman M , Cochrane GM
Published: November 2022

Unlike conventional methods, the interrupter method for measuring airway resistance is non-invasive and requires minimal patient co-operation. It can therefore be applied in critically ill patients, acute asthmatics, neonates, pre-school children, geriatric patients and unconscious patients. The method is based on transient interruption of airflow at the mouth for a brief period during which alveolar pressure equilibrates with mouth pressure. Measurement of mouth pressure is used to estimate alveolar pressure prior to interruption and the ratio of this to flow prior to interruption gives airway resistance. Using the interrupter method we have developed a portable device for measuring airway resistance which is simple to use and gives a direct instantaneous reading. Measurements of airway resistance obtained using the new device were compared with those obtained using conventional body plethysmograph methods in 43 adult patients. A close correlation was seen (r = 0.86). The two methods appear equally sensitive in detecting changes in airway resistance following bronchodilator therapy. The device has been used successfully in pre-school children unable to co-operate with conventional methods.
High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients
Authors: Lacronique J , Renon D , Georges D , Henry-Amar M , Marsac J
Published: November 2022

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.
The thermic effect of food in underweight patients with emphysematous chronic obstructive pulmonary disease
Authors: Green JH , Muers MF
Published: November 2022

Malnutrition and weight loss commonly occur in patients with the emphysematous type of chronic obstructive pulmonary disease (COPD), despite normal energy intakes. The present study was designed to assess energy expenditure, basal metabolic rate (BMR) and diet-induced thermogenesis (DIT) in ten patients with COPD, together with the oxidation rates of carbohydrate, protein and fat. The BMR was elevated when tested against the Harris-Benedict equation (p less than 0.001) or when compared with six age- and sex-matched controls (11.11 +/- 2.52 vs 8.12 +/- 1.31 kJ.h-1.kg muscle-1, p less than 0.05). The main difference in fuel oxidation rate was an elevated fasting fat oxidation rate in the patients compared with controls (8.31 +/- 3.09 vs 4.76 +/- 2.53 kJ.h-1.kg muscle-1, p less than 0.05). The overall thermic response to food (41.2 kJ.kg-1 liquid meal) as a percentage of energy intake was greater in the patients (49.5 +/- 6.3 vs 39.8 +/- 2.9%, p less than 0.01). The patients also displayed a greater post-prandial rate of protein oxidation as a percentage of protein intake than controls (56.9 +/- 18.5 vs 34.1 +/- 6.5%, p less than 0.05). These data suggest an increased energy cost of feeding and fasting in patients with the emphysematous type of COPD.