Proliferation is not increased in airway myofibroblasts isolated from asthmatics.

Airway mesenchymal cells, such as myofibroblasts and airway smooth muscle cells, contribute to inflammation, airway remodelling and hyperresponsiveness in asthma by excessive proliferation and inflammatory mediator production. Using endobronchial biopsies obtained from both nonasthmatic and asthmatic subjects, in situ proliferation was assessed by immunostaining for cyclin D1. The number of immunoreactive cells increased with asthma severity and was restricted to the epithelium and subepithelial connective tissue. Despite increases in smooth muscle area, cyclin D1 was not detected in cells in intact muscle bundles. Biopsy-derived cell cultures were characterised as predominantly myofibroblasts, and were assessed to determine whether proliferation and cytokine production varied with asthma status. Cell enumeration showed that basal proliferation was similar in cells from nonasthmatics and asthmatics, and mitogenic responses to fibroblast growth factor-2, thrombin or serum were either reduced or unchanged in cells from asthmatics. Interleukin (IL)-1-dependent granulocyte-macrophage colony-stimulating factor and IL-8 release was increased in cell supernatants from asthmatics. Thus, increased rates of cellular proliferation identified in situ in the asthmatic airway occurred outside the expanded smooth muscle compartment. Although reduced proliferative responses were observed in cultured myofibroblasts from asthmatics, the increased cytokine production by these cells suggests that this contributes to and may perpetuate ongoing inflammation in asthma.

Management of the acute attack of asthma in general practice.

Many acute attacks of asthma respond readily and completely to aerosol and/or parenteral bronchodilators, and subsequent management of asthma should try to prevent a further acute recurrence. Explanation of drug administration techniques and of the general nature of asthma are of great value in achieving good control. Severe, prolonged attacks require energetic measures, with transfer to units with intensive care facilities. These life-threatening situations are generally not hard to recognise.

Conscious perception of bronchospasm as a protective phenomenon in asthma.

Ten initially asymptomatic asthmatic subjects underwent methacholine-induced attacks of asthma on a number of occasions, to the point when tightness in the chest was just sensed (threshold point). As baseline lung volumes increased and the caliber of the airways decreased, the relative changes needed to attain a threshold point generally became smaller. Although pulmonary function can deteriorate chronically without increasing dyspnea, it is possible that a mechanism exists at the level of consciousness to protect a subject's breathing at times when pulmonary function is acutely impaired.

Bronchial provocation in the study of sensations associated with disordered breathing.

1. Lung volumes, airway resistance and flow/volume curves were measured in ten asthmatic subjects at times when tightness in the chest was just sensed (threshold symptom). 2. These measurements when the threshold symptom was induced by methacholine inhalation were compared with those when a similar symptom occurred spontaneously, in the same subjects. 3. Values during the methacholine-induced thresholds were very similar to those observed when threshold symptoms developed spontaneously. 4. Controlled bronchial provocation mimics spontaneous asthma sufficiently well to allow this technique to be used in the study of sensations associated with breathing. This has some advantages over the already established models utilizing external hindrances to breathing.

How mild is mild asthma?

Nineteen asthmatic volunteers underwent methacholine-induced asthma to the point when tightness in the chest was just sensed (threshold symptom). Changes in the following indices of lung function were measured--static lung volumes, forced expiratory volume in one second, and airways conductance. The increase in airways resistance necessary for threshold detection was at least double that previously reported in experiments using external resistive loads. Despite the mildness of the symptom, increases in lung volumes to the levels previously described during acute and severe asthma were occasionally found. It is emphasised that there may be little leeway in respiratory reserve between the development of minor and severe symptoms in some asthmatic patients.

Relationship between bronchial reactivity, airway caliber, and severity of asthma.

Indices of bronchial reactivity were obtained in 11 asthmatic subjects. These were based on the responses of specific airway conductance to timed cumulative doses of methacholine aerosol. The relationship of bronchial reactivity both to initial airway caliber and to current severity of asthma was then assessed. There was no correlation between initial airway caliber and the degree of bronchial reactivity for the group. Furthermore, a subject's bronchial response to methacholine, when expressed as a percentage of initial specific airway conductance, remained stable, even in the presence of moderate fluctuations in initial specific airway conductance. There was also no correlation between bronchial reactivity and severity of asthma for the group. Each subject's bronchial responses remained stable, even in the presence of moderate fluctuations in severity of asthma. These data confirm that a simple relationship between intrinsic bronchial reactivity and the severity of clinical asthma is not apparent.

Nasal challenge testing in grass pollen hay fever.

Nasal sensitivity to rye grass pollen allergens was evaluated by provocation testing in patients with hay fever due to grass pollen using measurements of nasal airways resistance (NAR), a reproducible system for delivery of allergen, and stringent criteria for allergen storage. Reproducibility was assessed in 24 subjects with hay fever by nasal provocation with serial dilutions of Lolium perenne allergens on 3 occasions: during the grass pollen season, immediately after the season, and in early winter. Threshold doses of allergen required to double the saline control NAR or to provoke persistent sneezing and rhinorrhea were slightly higher 1 mo after the pollen season, but there was no significant differences between threshold doses during the pollen season and 8 mo later. When the threshold doses during challenges were exceeded, there were late reactions in 4 of 24 patients. Normal subjects and patients with perennial rhinitis and with negative skin tests to L. perenne extract were unresponsive in nasal challenge tests.

Intravenous erythromycin in acute chest infections in critically ill patients.

Superinfections with resistant micro-organisms have recently become an increasing problem in hospital patients and are throught to be contributed to by inappropriate use of newer, broad-spectrum antibiotics. Erythromycin exhibits a more limited spectrum of antibacterial activity and was therefore re-evaluated in the treatment of acute chest infections in critically ill patients. Twenty-one patients were given erythromycin in a dose of 1.8 g per day by continuous intravenous infusion for up to five days. A satisfactory clinical response occurred in ten patients, in all of whom erythromycin-sensitive micro-organisms were isolated from sputum. An unsatisfactory response occurred in six patients, all associated with micro-organisms insensitive to erythromycin and requiring alternative antibiotic treatment. No undesirable side-effects were noted. It is concluded that erythromycin is a safe and useful agent in the routine treatment of acute chest infections in critically ill patients.

Perception of asthma.

Subjective assessment and objective measurements of airways obstruction were compared in 82 patients during methacholine-induced asthma. 15% of the patients were unable to sense the presence of marked airways obstruction (forced expired volume in 1 s less than 50% of the predicted normal value). These subjects could not be characterised as a distinct group on the basis of their sex, age, or duration of their asthma. This reinforces the need for objective measurement of lung function in the management of asthma.

Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung.

An isolated perfused canine lung preparation in which determinants of vascular caliber could be individually controlled was developed. The relation of pulmonary arterial (Pa), venous (PV), and alveolar (PA) pressures was such that Pa greater than PA greater than PV throughout the whole lung. The addition of isoprenaline to the perfusate abolished vascular reactivity. Once stability was reached, vascular cross-sectional area remained acceptably constant for 2.25 hours as judged by normalized conductance. The influence of perfusate hematocrit, blood gas tensions, and pH on pressure-flow relations was then studied in 15 isolated canine lungs. The hematocrit-vascular conductance relation was derived at constant perfusion pressure. Conductance varied linearly with hematocrit over a range of 16.5 to 89.5%. Mean pulmonary arterial blood gas tensions were: PO2 = 121 mm Hg, PCO2 = 28 mm Hg, and pH = 7.46. Acute respiratory acidosis (PO2 = 30 mm Hg, PCO2 = 81 mm Hg, pH = 7.17) and lactic acidosis and hypoxemia (PO2 = 32 mm Hg, PCO2 = 21 mm Hg, pH = 6.96) did not significantly alter this relation. Transformation of the conductance-hematocrit data indicated that hematocrit was the most important determinant of relative apparent viscosity of the blood. Both acute respiratory and lactic acidosis failed to significantly increase relative viscosity within the range of hematocrit usually found in secondary polycythemia.

Respiratory disability in workers' compensation claimants.

This study was designed to examine whether claimants for compensation for work-related respiratory impairment due to chronic airflow obstruction exhibited greater symptoms of disablement than other patients with similar obstruction. It also sought evidence of bias, either towards or against the claimants, by the medical examiners. One hundred and twenty-eight subjects (68 claimants) with chronic asthma, chronic bronchitis, and emphysema were studied. There was a reasonable concordance of subjective judgements between patients and medical examiners in 81% of the disabled workers, and in 90% of the other medical group. Similarly, impairment of lung function (FEV1/VC ratio) in both groups was comparable at most levels of subjective disability. It was concluded that, in contrast to some previous reports, claimants for compensation for work-related chronic obstructive airway diseases did not tend to exaggerate their disabilities. This does not imply that the claimants' ailments were necessarily occupation-related.

Intranasal immunotherapy and polymerized grass pollen allergens.

The effects of immunotherapy by intranasal insufflation of Lolium perenne allergens modified with glutaraldehyde (Glu-Rye) was tested by a stratified placebo-controlled trial in 16 adult subjects with hay fever. The purpose of this pilot study was to determine whether the treatment could reduce nasal sensitivity to allergen in provocation tests. Modification of the allergen was shown to include polymerization and reduced allergenicity, but retained immunogenicity. Nasal sensitivity to unmodified L. perenne allergens was measured by threshold-type quantitative nasal challenge and posterior rhinometry for measurement of nasal airway resistance. In challenge tests after a 10-week course of intranasal preseasonal treatment with Glu-Rye, nasal sensitivity was reduced, but this effect was not maintained when testing was repeated 9 months after treatment. Post-seasonal serum levels of IgE antibodies to L. perenne were also not significantly affected by the treatment.

Maximal mid-inspiratory to maximal mid-expiratory flow rate ratio in upper airway obstruction.

The maximal mid-inspiratory to maximal mid-expiratory flow rate ratio (MMIF/MMEF) was measured in 16 patients with upper airway obstruction, in eight with pleural disease, in 25 with chest wall abnormalities, in 64 with various lung diseases and in 28 normal subjects. MMIF/MMEF ratio values of less than 1.0 were recorded in eight out of 16 patients with upper airway obstruction, in nine out of 25 patients with chest wall abnormalities and in one normal subject. Our findings show that a MMIF/MMEF ratio less than 1.0 although suggestive, is not diagnostic of upper airway obstruction. However, reduced MMIF/MMEF ratio in the presence of airflow obstruction is specific in localizing obstruction to the upper airway.

Estimation of P50 from a single venous blood sample.

The oxygen tension at 50% saturation of haemoglobin, or P50 was calculated from a single O2 tension and saturation measurement on a venous blood sample by means of the proportional displacement assumption of Severinghaus and a parallel displacement assumption. These calculations were compared with a two-point technique, based on Hill's formula, which was assumed to be accurate. The results obtained from the simpler, one-point techniques correlated well with the more complex two-point estimation. This correlation remained for subjects with normal, high, and low P50.

Action of tilidine hydrochloride and morphine hydrochloride on ventilatory control in normal subjects.

The action of tilidine hydrochloride and morphine hydrochloride on the ventilatory response to inhaled carbon dioxide has been assessed in 10 normal volunteers. In doses of 50 mg and 100 mg given intravenously, tilidine hydrochloride induced less respiratory depression than 10 mg of morphine given intravenously. Side effects were not different or troublesome with either drug. Depending on its relative pain-relieving property, tilidine hydrochloride may have advantages over morphine as an analgesic.