Tolerance of carprofen in patients with asthma caused by non-steroidal anti-inflammatory drugs.

Eight asthmatics with respiratory intolerance to NSAIDs and two subjects (one asthmatic, one healthy) only sensitive (asthma) to pyrazolone drugs were challenged under single-blind conditions with a new NSAID, carprofen. No adverse effects were observed in patients sensitive to pyrazolones. Among the other patients, only three developed considerable bronchial obstruction which was rapidly reversed by inhalation of a beta 2-stimulant (fenoterol: 2 puffs). Two subjects developed nasal obstruction with rhinorrhoea: in conjunction with bronchoconstriction in one patient and alone in the other. In conclusion, acute administration of carprofen in patients with respiratory intolerance to NSAIDs, in contrast to most other NSAIDs, never creates a situation of real danger even though in some patients it may considerably increase nasal and bronchial resistance.

[Changes in the acid-base equilibrium and the water-electrolyte balance during maximum aerobic work in patients with chronic broncho-pulmonary disease]. / Contributo alla conoscenza delle modificazioni dell'equilibrio acido-base ed idroelettrolitico in corso di lavoro aerobico massimo (LAM) nel broncopneumopatico cronico.

The Authors studied the behaviour of acid-base balance in subjects with chronic obstructive lung disease undergoing Maximal Aerobic Work following the method of Pasargiklian e Coll., 1955. For the research two different experimental pattern were adopted: 1) patients were subjected, in two different sessions, to the muscular work in room air and in hyperoxia (60%) breathing for the evaluation of acid-base balance. During hyperoxia Authors observed rising of paO2 and decrease of paCO2, pH and lactic acid concentration. 2) In the second pattern the muscular test was performed in room air only with the use of an antiphosphodiesterasic drug e.v. administration in each patient. Together with acid-base balance behaviour of plasmatic electrolytic assessment was controlled in order to evaluate adaptation to work. The data, although preliminary, show an increase of paO2 with decrease of paCO2 in both test; potassium and bicarbonates concentration increase more in the first test without theophyllin whereas this drug forbid these increments. The Authors even if the experimental program must be developed suggest that the evaluation of these data is interesting in diagnosis and prognosis in chronic lung disease for the cellular adaptation to work and offers interesting elements to carry on the rehabilitation of chronic obstructive lung disease.

[The treatment of acid-base imbalance in the intensive care of respiratory diseases]. / La terapia del disequilibrio acido-base nel trattamento intensivo della patologia respiratoria.

After giving an outline of pneumogenic respiratory insufficiency, signally that deriving from chronic obstructive bronchopulmonary disease, the Authors describe the intensive care of respiratory insufficiency, first from the anesthesiologist's point of view and then in a broader medical sense. In regard to the latter, the Authors emphasize the importance of material equipment and staff training and teamwork; they also list a number of possible iatrogenic disorders in intensive care. Next they discuss medical aids and more specifically the machinery designed to assist respiration, such as pulmonary ventilators and the "iron lung", as implements that can be used to advantage in medical wards. Then they describe the elements to be used for a correct assessmnet of the severity of respiratory insufficiency, under the following subheadings:--state of coma, if present;--state of acid-base balance, oxemia, and water and electrolyte balance;--circulatory compensation or failure;--need for correcting bronchial obstruction. Through several representative examples concerning the medical correction of alterations of CO2, pH, electrolyte composition, and water and blood volumes, they describe the therapeutic measures to be undertaken particularly as regards the metabolic sequels (alkalosis or acidosis) that may occur in the course of treatment. Coming next to intensive care utilizing mechanical devices, they stress the importance of monitoring the parameters of humoral balance during (and even more so, after) said treatment, in view of avoiding the emergence of iatrogenic disturbances such as the reventilation syndrome and the syndrome of post-hypercapnic metabolic alkalosis.

Perspectives in the treatment of reversible airway obstruction.

The pharmacological therapy of asthmatic syndromes is based essentially on the programmed use of disodium cromoglycate, beta-2-stimulants, antimuscarinics, theophyllines and corticosteroids. However, the continual progress being made in pathogenesis and pharmacology suggests, to an ever-increasing extent, the application of new therapeutic approaches for these diseases, some of which are fairly interesting from a speculative point of view although they are as yet of limited practical value. Calcium antagonists and alpha-blockers have a mild anti-reactive effect but this is not sufficiently potent to justify use of these products in the treatment of asthma unless there are also cardiovascular disorders for which these drugs are particularly indicated. Despite the initial promising prospects, all attempts to obtain PGE analogues of therapeutic value as antiasthmatics have proved fruitless. Research into orally active chromone derivatives has proved equally unproductive. On the other hand, certain new inhalatory chromones are decidedly more promising. Specific antagonization of mediators (histamine, prostaglandin, leukotrienes) did not produce the effect hoped for in asthma, but this was foreseeable insofar as the major pathogenic mediators are too vast in number (and no doubt there are still many more to be discovered) to allow one to conceive it possible to achieve a satisfactory therapeutic effect by merely blocking some of them. Inflammation of the bronchial wall is currently considered to be one of the basic pathogenic factors provoking the recurrence of asthma: this is proved indirectly by the potent antiasthmatic effect of corticosteroids which are the most effective anti-inflammatory agents. As regards nonsteroidal anti-inflammatory drugs (NSAID), however, matters are more complicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, functional and pathogenetic aspects of bronchial reactivity to prostaglandins F2alpha, E1, and E2.

Based on our results and on those reported in literature, we may draw the following conclusions. As a rule, asthmatic patients are markedly more sensitive than normal subjects to the bronchoconstrictive action of PGF2alpha by aerosol. However, the individual response is quite variable, which predicts and justifies some exceptions. On this subject, we found a peculiar exception in a female patient with extrinsic asthma, who tolerated abnormally large amounts of PGF2alpha. In contrast, we found a normal subject, who developed a bronchial hypersensitivity to PGF2alpha of frankly asthmatic type, following a moderate postinfluenzal bronchitis. Intravenously PGF2alpha loses the most part of its bronchoconstrictive effect, probably because it is rapidly metabolized before it may reach the bronchial receptors involved in the bronchospastic response. On the contrary, the action on vascular smooth muscle of the pulmonary circulation is evident, just because it is reached before the above transformation, mainly performed by 15-PG-dehydrogenase. An important component of the PGF2alpha-induced bronchospasm, although varying individually, is surely nonspecific, as it is shown by the protection obtained with an atropine-like agent. The moderate but significant protection obtained with DSCG, may be interpreted in a way similar to the one exerted again by DSCG on other nonspecific stimuli. Since indoramine has no effect in preventing PGF2alpha-induced bronchospasm, the intervention of bronchial alpha-receptors in the pathogenesis of this type of bronchospasm may be excluded. Nonsteroid antiinflammatory agents do not seem to change in asthmatic patients bronchial reactivity to PGF2alpha, as was found recently with other specific and nonspecific stimuli. Our studies do not modify current thought regarding the poor present therapeutic value of PGE as bronchodilator agents. Prospects are no better with the stereoisomer of PGF2alpha, PGF2beta (41), with endoperoxides PGG2 and PGH2 (42) and with the analogues 15-methyl-PGE2, 15-epi-PGA2, and 8-iso-PGE1 (43). However, it is reassuring that, even in the absence of a demonstrable bronchodilator effect, both PGE1 and PGE2 are capable to prevent in a large degree the specifically and nonspecifically induced bronchospasm.

Prevention of exercise-induced bronchoconstriction by inhaled frusemide.

To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications.

Aspects of bronchial reactivity to prostaglandins and aspirin in asthmatic patients.

The behaviour of bronchial reactivity to PGF2alpha was studied in asthmatic patients under various experimental conditions. Premedication with aminophylline, i.v., and, to a lesser extent, with DSCG afforded a partial protection, while beclomethasone dipropionate was inactive under this point of view. Diftalone, a new non-steroid anti-inflammatory agent, was well tolerated in 9 aspirin-intolerant asthmatic patients, and did not modify the bronchial response to PGF2alpha which was found to be generally lower then that of other aspirin-tolerant asthmatic patients. PGE 1-2 and DSCG prevented the bronchospasm induced by inhalation or ingestion of acetylsalicylic acid in a small group of patients. Good protection was also reached with PGE1-2 in the exercise-induced bronchospasm.

Classification of respiratory functional impairment in chronic obstructive pulmonary disease.

Starting from a paper published in 1964 by Wilson et al., we explored the possibility of classifying the clinical and functional deficit of patients with chronic obstructive lung disease into six classes, class 0 representing normality and class 5 greatest severity. Each symptom or sign was classified into six degrees of increasing severity. Next, we looked for a possible dependence of the collegially assigned score on anthropometric, clinical, or instrumental data in each case. More particularly, we tried (1) to identify such combinations of variables as would permit classification of the patient with the smallest possible error, and (2) to determine which of the variables reflected the severity of the case more faithfully. The results emerging from this study suggest the possibility of evaluating and classifying respiratory impairment in three different ways, as follows: (1) On the basis of clinical data only. This method is the easiest to use and affords a fairly good determination coefficient (R2 = 0.812). (2) Using only some combinations of laboratory data (static and dynamic pulmonary volumes, blood gases, etc.), with or without the addition of vital statistics and anthropometric data. These subensembles would allow a posteriori estimates in cases where the subject is no longer available for questioning and examination. In that case the best multiple regression affords a determination coefficient R2 = 0.82. (3) Using all clinical and laboratory data available. In that case, the best multiple regression (R2 = 0.899) for predictive purposes is that which includes the sum of clinical data, the pulmonary volumes before and after pharmacological bronchodilation, and the PaCO2 value. For practical purposes, however, the most convenient function is the one that includes the sum of clinical data plus FEV1 and RV (R2 = 0.863). Even with the best of the three functions proposed in this paper, however, the standard error of estimate entails tolerance limits sometimes amounting to one whole class of severity. Still, the probability of making an error exceeding one class of severity occurs in only 3.7% of the cases, an average which seems quite acceptable from the clinical point of view.