Pneumonitis complicating methotrexate therapy for pustular psoriasis.

We report a patient with pustular psoriasis who developed interstitial pneumonitis after receiving weekly methotrexate (MTX) therapy at an average dose of 20 mg for 26 years. The patient responded dramatically to withdrawal of the drug and administration of corticosteroids. Pulmonary toxicity is a rare adverse effect of MTX therapy and is particularly uncommon in psoriatics. As interstitial pneumonitis is a potentially fatal but reversible complication, early respiratory symptoms even in patients on low-dose MTX treatment should be appropriately investigated.

Pulmonary arterial hypertension and emphysema.

Pulmonary artery pressures were estimated by an indirect method using echocardiography (Boyd et al. 1980), in a group of patients with chronic airflow obstruction, in order to investigate the degree of pulmonary hypertension in patients with emphysema. We found a positive correlation between the estimated pulmonary artery end diastolic pressure (PAEDP) and the radiological emphysema score (r = 0.58, P less than 0.005), and between the estimated PAEDP and the transfer constant for carbon monoxide (KCO) (r = 0.66, P less than 0.002). There was no correlation between the PAEDP and the arterial partial pressure of oxygen (PaO2) before exercise, between the PAEDP and the change in oxygen partial pressure after exercise, or between the KCO and the PaO2. It is suggested that emphysema does predispose to pulmonary arterial hypertension and that the relationship is probably secondary to vessel destruction rather than hypoxia.

Effects of prostaglandins E1, E2, and F2 alpha on mucin secretion from human bronchi in vitro.

The effects of three prostaglandins on the output of 35S labelled mucus glycoproteins (mucins), from explants of human bronchial tissue suspended in Ussing chambers, have been investigated. Prostaglandin F2 alpha, added to the Krebs-Henseleit solution bathing both luminal and submucosal sides of the tissue, significantly increased mucin output at concentrations of 0.1 and 1.0 micrograms/ml (0.28 and 2.8 microM), 11 preparations being used for each dose. Since prostaglandin F2 alpha has been shown to be released from human airways challenged by antigen, it may be important in the regulation of mucus secretion in these circumstances. Prostaglandins E1 and E2 had no significant effects on mucin output even at the highest concentration (1.0 micrograms/ml), though in half the tissues tested PGE2 stimulated secretion consistently. These results contrast with the findings in a previous study, which showed an inhibition of mucin output by PGE2.

A preparation for the study of secretory function of the human bronchus in vitro.

Bronchi, not involved in tumor, were removed from resected human lungs. They were mounted in Ussing chambers containing Krebs-Henseleit solution with radiolabelled precursors of mucus. Airway was examined by both light and electron microscopy. Tissues recently removed from resected lungs exhibited both intra- and extra-cellular oedema and hypoxic changes in mitochondria, but tight junctions between epithelial cells appeared intact, indicating an effective epithelial barrier. Tissues removed from Ussing chambers after up to 6 h showed little oedema and their mitochondria were normal. Their appearance had returned to that of specimens taken that biopsy and fixed immediately. Autoradiographs of specimens from Ussing chambers showed that the mucus-producing cells had concentrated the radiolabels . Mucus in gland ducts was also radiolabelled. Damaged areas of mucous membrane were rare and probably pre-operative. We conclude that resected bronchi, suspended in Ussing chambers, have a structure and secretory activity suitable for investigations of the control of secretion.

Action of serum on the output of secretory glycoproteins from human bronchi in vitro.

The effect on mucin output of placing dilute serum from healthy donors in contact with the luminal surface of human airway has been studied. Bronchi were dissected from lungs removed at operation. Mucins, radiolabelled biosynthetically, were collected from the luminal aspect of the bronchi, which were mounted in Ussing chambers. Serum added to the luminal aspect of the tissue, at dilutions ranging from 1:100 to 1:10 of Krebs-Henseleit solution, consistently increased the output of radiolabelled mucins. The concentrations of serum tested in these experiments lie within the range commonly found in sputum coughed from the lungs of those with inflamed airways. Serum diluted to 1:2500, which is roughly the concentration found in the normal human airway, had little or no effect on bronchial secretion. Increased leakage of serum into the inflamed airways is suggested as one of the stimuli that increase bronchial secretion.

Laser treatment for carcinoma of the bronchus.

Laser treatment in carcinoma of the bronchus is essentially palliative and is suitable for only a few patients. Patients selected for laser treatment must have predominantly endobronchial growth with normal bronchial anatomy still identifiable and symptoms due to the obstruction or to haemoptysis. A total of 34 patients with carcinoma of the bronchus were treated with argon gas or neodynium yttrium aluminium garnet crystal lasers. Good palliation was obtained in just over half the cases of partial obstruction of the trachea or main bronchus, but best results were obtained in lesions of the trachea or main carina. Re-expansion of the collapsed lung was achieved in some cases but with considerable risk of pneumonia. Haemoptysis was controlled at least partly in several cases. Laser treatment has the advantage of having no toxicity or dose limit and may be used in cases of poor respiratory function. The procedure was better tolerated than radiotherapy or chemotherapy and its relatively lower cost may justify setting up laser units in major cities.

Analyses of human tracheobronchial mucus from healthy subjects.

Tracheobronchial mucus was obtained from four healthy subjects by fibreoptic bronchoscopy. The material was fractionated by gel exclusion chromatography on a Sepharose CL2B column. One peak of optical density 280 nm was found in the excluded volume and another in the included volume suggesting that these contained the majority of the aromatic amino acids. Alcian Blue was used to precipitate acidic glycoproteins in each fraction. When the dye had been redissolved two peaks of optical density at 620 nm were detected, in the excluded and included volumes respectively, and these peaks corresponded with the absorbance at 280 nm. The elution profiles were similar to those given by mucins from other systems. Treatment with urea and dithiothreitol caused no change in the elution profile so there is no evidence that disulphide bonds link glycoprotein subunits in airway mucus from healthy subjects.

Sympathomimetic drugs stimulate the output of secretory glycoproteins from human bronchi in vitro.

1. We describe a method for supporting pieces of human bronchi in Ussing chambers, for radiolabelling the contents of the secretory cells with 35S, and for collecting radiolabelled macromolecules secreted on to the luminal aspect of the tissue. This method has previously been used to study airway secretions in animals [R. J. Phipps, J. A. Nadel & B. Davis, American Review of Respiratory Disease, (1980) 121, 359-365]. Evidence is given that the radiolabelled molecules are secretory glycoproteins, probably mucus glycoproteins. 2. Phenylephrine, an alpha-adrenoceptor agonist, increased the rate at which the bronchi secreted radiolabelled glycoproteins. Thymoxamine, an alpha-adrenoceptor antagonist, blocked this effect but propranolol, a beta-adrenoceptor antagonist, did not. 3. Dobutamine, a beta-adrenoceptor agonist, increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this but thymoxamine did not. 4. Salbutamol, a beta 2-adrenoceptor agonist, also increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this effect. 5. We conclude that both alpha- and beta- adrenoceptor agonists increase the rate of glycoprotein secretion in human bronchi in vitro and that this almost certainly means that they increase the rate of mucus secretion.

Diaphragmatic breathing training and walking performance in chronic airways obstruction.

Eight patients with chronic obstructive bronchitis and moderate disability entered a pilot study of the effects of controlled diaphragmatic breathing. They received three weeks of placebo physiotherapy (shoulder exercises) followed by three weeks of instruction on controlled diaphragmatic breathing. No beneficial effects were observed on exercise performance or the perceived strain of exercise.

Echocardiographic method for the estimation of pulmonary artery pressure in chronic lung disease.

The prognostic implications of pulmonary hypertension in chronic lung disease, and the difficulty in establishing its severity without cardiac catheterisation, indicate the need for a reliable non-invasive method of assessing the pulmonary artery pressure. It is likely that the time taken by the right ventricle to generate a sufficiently high pressure to open the pulmonary valve will increase progressively as the pulmonary arterial diastolic pressure rises. Therefore, the time interval between closure of the tricuspid valve and opening of the pulmonary valve has been obtained by high-speed echocardiographic recordings of the tricuspid and pulmonary valves in a group of 17 patients with chronic lung disease. Each patient underwent right heart catheterisation immediately after the echocardiographic examination so that the pulmonary arterial diastolic pressure could be obtained directly. A range for the group from 15 mmHg (2.0 kPa) to 45 mmHg (6.0 kPa) was observed. The linear correlation between the measured diastolic pressure and time interval from the tricuspid valve closure to pulmonary valve opening was highly significant (r = 0.94, p = less than 0.001) and the scatter was relatively small. It is therefore suggested that this time interval, obtained non-invasively by echocardiography, can be used as an index of the severity of pulmonary hypertension associated with chronic lung disease.

Corticosteroids in chronic airways obstruction: can the patient's assessment be ignored?

In a study to examine the methods of assessing the response of patients with chronic airways obstruction to corticosteroids, 20 patients received a week of placebo tablets, followed by three weeks of prednisolone 30 mg daily. Subjective benefit was assessed by a visual analogue scale (VAS), and objective changes by spirometry and an exercise test. Significant increases in FEV1 and in exercise performance were observed after steroid therapy. Changes in FVC correlated both with VAS score and with changes in exercise performance. Changes in FEV1 correlated with neither. The good correlation between the changes in a ventilatory function test (the FVC) and the patients' assessments of the drug suggests that the non-specific euphoriant effect of steroids does not eclipse their specific action on ventilatory function. Assessment of benefit should include a subjective assessment and changes in FVC and exercise performance. Changes in FEV1 appear to have less clinical relevance.

Can patients keep their own peak-flow records reliably?

Fifty patients recorded their peak expiratory-flow rate (P.E.F.R.) in hospital, unaided by nursing staff, five times a day for 5 days. Each patient's readings were randomly and independently checked on two occasions during this period. 69% of checked readings were accurate. Most patients kept satisfactory records as a table, but were less efficient in recording their results on a P.E.F.R. chart. Recording of P.E.F.R. by patients with respiratory disease saves nursing time and provides valuable clinical information.

The effects of oral propranolol and metoprolol on lung function and exercise performance in chronic airways obstruction.

Fifteen men with chronic airways obstruction received a test dose of propranol 20 mg orally. Six developed increased breathlessness. Nine who tolerated the test dose received metoprolol (100 mg) and propranolol (80 mg) on different days in a randomized double-blind fashion. Changes in resting and exercise heart rate, spirometry and exercise tolerance were measured 1 and 6 hours later. The drugs had similar effects on heart rate. Propranolol, but not metoprolol, caused significant reduction in forced expiratory volume in one second (FEV1) and peak expiratory flow rate. Neither drug produced significant changes in forced vital capacity (FVC) or exercise performances in the group as a whole, although the range of changes was wide. Despite considerable reduction in FEV1 and FVC in some individuals, most reported no increase in symptoms. Changes in exercise tolerance at 1 hour correlated significantly with changes in FVC but not with those in FEV1. It is proposed that changes in FEV1, though of pharmacological interest, may be less relevant clinically than changes in FVC.

The sympatomatic treatment of carcinoma of the bronchus using combination chemotherapy.

A study was made of chemotherapy for inoperable carcinoma of the bronchus. Only patients with symptoms directly due to the tumour or with evidence of rapid tumour growth were selected for treatment. Half the patients selected in this way responded and in these patients survival may have been prolonged. The regimen chosen caused the minimum of interference with the patient's life and, by relief of symptoms, appeared to offer an improvement in the quality of life.