A review of microvascular measurements in wound healing.

The microcirculatory evaluation in patients affected by arteriopathic or venous ulcers is usually carried out using laser Doppler flowmetry, transcutaneous oxygen (transcutaneous pressure of oxygen, TcPO(2)), and carbon dioxide (transcutaneous pressure of carbon dioxide, TcPCO(2)) measurements and capillaroscopy. These techniques provide significant pathophysiologic and prognostic information. TcPO(2) and TcPCO(2) diagnose and classify the extent of arterial disease in the leg ulcers caused by arterial disease; the prognostic value is recognized, though doubts about its prognostic potential exist in the case of leg ulcer. Laser Doppler flowmetry is able to identify the first functional impairment in the early stages of the arterial disease and in the complicated venous insufficiency. Capillaroscopy gives us morphological and quantitative parameters of the capillary bed that is damaged in arteriopathic and venous ulcers; nevertheless, it does not provide us with definite prognostic indexes. Combining the 3 methods may contribute to yield objective measures in the clinical management of lower extremity ulcers.

Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short- and long-term therapeutic management of non-reconstructable lower critical limb ischemia?

AIM: The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS: In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Long-term clinical outcomes in critical limb ischemia--A retrospective study of 181 patients.

OBJECTIVE: Critical limb ischemia (CLI) is the most severe manifestation of the peripheral arterial disease. To date, several prognostic factors have been identified but the data of long-term follow-up in real life setting are scarce. The aim of our study is to describe a large group of CLI patients and identify possible prognostic factors, in a long-term follow-up. PATIENTS AND METHODS: Case-control, retrospective study. 181 consecutive CLI patients with a minimum follow-up of 5 years were included in the study. RESULTS: Overall mortality was 15%, 24%, and 43% at 1, 2, and 5 years, respectively. Among known risk factors, only arterial hypertension was significantly correlated with survival rate; no differences were found between diabetics and non-diabetics. Patients treated with intravenous iloprost (46%), compared to untreated patients, showed a better (p < 0.0001) long-term outcome in terms of major amputation (6% vs. 21%), subsequent vascular surgery (4% vs. 32%) and survival rates (69% vs. 47%), at 5-year follow-up. Major amputations were significantly correlated with lower median forefoot transcutaneous values of O2 (0/3 mmHg, p < 0.001) and higher median values of CO2 (83/53 mmHg, p < 0.0001) in supine/dependent position, respectively. CONCLUSIONS: Our results confirm the poor prognosis of CLI patients in a very long-term follow-up and the severe metabolic damage caused by ischemia. A favourable role of iloprost was observed, in agreement with previous evidence in the literature.

Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients.

OBJECTIVE: Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ. PATIENTS AND METHODS: A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years. RESULTS: 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p < 0.05) and in non-responders compared to responders (60 vs. 49 mmHg; p < 0.05). TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0.05). CONCLUSIONS: Our results confirm the favourable role of iloprost on the long-term outcome in patients with CLI. In particular, the maximum benefit is obtained in responder patients treated with multiple cycles of infusion.

Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. METHODS: 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. RESULTS: Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. CONCLUSIONS: Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.

Calcium channel blockers blunt postural cutaneous vasoconstriction in hypertensive patients.

The aim of this work was to test whether calcium channel blockers interfere with skin vasoconstrictor reflexes that minimize postural increases in capillary pressure and avoid fluid extravasation and eventually subcutaneous edema. Studies were conducted in 23 untreated mild to moderate essential hypertensives; drugs, either calcium channel blockers or not, were given for 2 weeks according to a crossover, sequence-randomized design. Skin blood flow was measured by laser Doppler flowmetry in two skin areas: (1) the dorsum of the foot, where arteriovenous anastomoses are poorly represented, and (2) the plantar surface of the great toe, where those anastomoses are predominant. Determinations were obtained both with the foot at heart level and with it placed passively 50 cm below the heart level; percent flow changes from the horizontal to the dependent position were the measure of postural vasoconstriction. Two dihydropyridine derivatives, amlodipine (10 mg UID) and nifedipine (60 mg UID), and verapamil (240 mg BID), a chemically unrelated compound, diminished to similar extents the postural fall in skin blood flow at the dorsum of the foot. Blockade of alpha1-adrenergic and AT-1 subtype angiotensin II receptors by doxazosin (4 mg UID) and losartan (50 mg UID), respectively, exerted no effect. Postural skin blood flow responses at the plantar surface of the great toe were unmodified during the pharmacological trials. Thus, calcium channel blockers of different chemical origins antagonized postural skin vasoconstriction at the dorsum of the foot. The data indicate altered postural capillary blood flow regulation, since arteriovenous anastomoses are anatomically absent at this site; the effect was independent of either alpha1-adrenoceptor or angiotensin II receptor antagonism. Interference with skin postural vasoconstrictor mechanisms may result in net filtration of fluid to the extravascular compartment. This mechanism might explain the as yet unknown pathogenesis of ankle edema during treatment with calcium antagonists.

Forearm blood flow reserve and cardiac and renal indexes of pressure load in normotensive and hypertensive individuals.

In response to hypertension, arterioles remodel their structure, the heart develops myocardial hypertrophy, and the kidney reduces creatinine clearance and increases albuminuria. To better understand the interrelations among the target organs involved in hypertension, we evaluated minimal forearm vascular resistances--a hemodynamic index of arteriolar structure derived from mean blood pressure and maximal postischemic forearm blood flow--the echocardiographic indexes of cardiac structure, and urinary albumin excretion and creatinine clearance in 29 male mild to moderate non-macroalbuminuric essential hypertensive patients on no drugs and 11 age- and sex-matched normotensive control subjects. Minimal forearm resistances were elevated in hypertensive patients and correlated with left ventricular mass, wall thickness, and mean arterial pressure. Patients with abnormal minimal forearm resistances (2 SD above normal) were characterized by higher pressure, greater wall thickness, lower creatinine clearance, and higher albumin excretion, suggesting that maximal forearm flow capacity does relate to the hemodynamic load exerted on both the kidney and heart. However, the correlation with cardiac structure and mean arterial pressure explained only part of the variability of minimal forearm resistances. Furthermore, no correlation among these parameters was found when hypertensive patients were evaluated separately from normotensive subjects, possibly because of heterogeneous factors active on arteriolar structure and unrelated to the pressor load. Overall, the data suggest that the development of abnormal minimal forearm resistances in the course of the hypertensive process is related to the pressor load, but its details need further understanding.

Congestive heart failure in elderly patients: controlled study of delapril versus captopril.

In this controlled trial, 30 elderly patients with congestive heart failure, New York Heart Association (NYHA) classes II and III, were randomly assigned to treatment with captopril 25 mg three times daily or delapril 15 mg twice daily. At the end of an 8-week treatment period, clinical symptoms of heart failure were significantly relieved by both drugs, with a consistent and statistically significant improvement in patients' quality of life evaluated using a symptoms/activity scale (p < 0.001). None of the patients was judged NYHA class III at the end of the trial and 40% were assigned to class I (p < 0.01). There was a relevant, but not statistically significant, increase in exercise duration in both treatment groups (10% captopril group, 14% delapril group), but the number of patients discontinuing the exercise test for dyspnea was 50% less in the delapril group. Neither drug had evident effects on echocardiographic left ventricular parameters. Two patients treated with captopril and 3 with delapril complained of mild-to-moderate adverse reactions. The safety of both drugs was confirmed by laboratory tests.

Pulmonary embolism: epidemiology.

Present evidence suggests that venous thromboembolism is the third most common acute cardiovascular disease after cardiac ischemic syndromes and stroke. The frequency of the diagnosis of pulmonary embolism (PE) at a given hospital greatly increases if a referral unit for PE is set up in the hospital. Pulmonary embolism is characterized by a continuous spectrum of severity, from 2 to 3 to 15 to 16 embolized pulmonary segments (over a total of 19). Morbidity from PE increases with age and male sex (males/females ratio: 1.24). In only a minority (10%) of patients with PE and/or deep-vein thrombosis (DVT), primary deficiencies of coagulation-inhibiting proteins have been shown. Primary abnormalities of the fibrinolytic system seem even more rare. On the basis of the clinical conditions preceding the embolic episode, patients may be divided into different groups: apparently primary or idiopathic PE (40%), surgery or trauma (43%), heart disease (12%), neoplastic disease (4%), and systemic disease (1%). Patients with apparently primary or idiopathic PE often develop subsequent clinically overt cancer (9.1%), whereas surgery or trauma patients rarely do (1.4%). Furthermore, the former exhibit a significantly shorter survival than the latter mostly for causes of death that reflect increased predisposition to thrombogenesis. Thus, as for DVT, it is convenient to consider a primary or idiopathic form also for PE.

Transcutaneous oxygen tension measurement in patients with chronic arterial obstructive disease: reliability and long-term variability of the method.

Although transcutaneous oxygen tension (TcpO2) measurement may be useful for assessing changes in regional perfusion induced over time by drug or surgical treatment in patients with chronic arterial obstructive disease (CAOD), the reliability of the method over a long-term period is not know. To approach this problem, the authors evaluated retrospectively the behavior of TcpO2 measurement over time in patients with CAOD. To eliminate confounding influences due to the concomitant vascular disease at the limb level, data analysis was performed on TcpO2 measured at the right infraclavicular position. The median length of follow-up ranged from twenty days in 34 patients to 832 days in 3 patients (n = 2 and n = 10 individual sequential replications respectively). Initial and final TcpO2 values did not differ significantly even at the longest follow-up term, which indicates that the parameter is constant over time. The intrapatient variation coefficient of TcpO2 (calculated over at least three individual replications) ranged between an average of 11% to 16.2%. The corresponding interpatient variation fluctuated between 15.5% and 33.4%, a variability explained to some extent by sex-related influences, but, at least in the range of this sample, not by age, arterial oxygen levels, or disease status. Thus TcpO2 levels per se are stable, implying that TcpO2 measurement has the potential to record consistent changes caused by specific therapeutic interventions or the clinical evolution of patients with CAOD. However, the intrapatient and interpatient variability of the method has to be taken into account when TcpO2 is used for the follow-up and the physiopathologic study of patients with CAOD.

Acetylcholine-mediated vasodilatation and tissue-type plasminogen activator release in normal and hypertensive men.

Muscarinic agents release tissue plasminogen activator (t-PA) in the forearm circulation of normal subjects, but no information exists about their effect in those hypertensive patients in whom the response to endothelial-mediated vasodilators is blunted. Acetylcholine, an endothelium-dependent vasodilator and a muscarinic agonist that releases t-PA from in-vitro systems, and sodium nitroprusside, an endothelium-independent vasodilator, were infused into the brachial artery at rates calculated to cause a similar degree of vasodilatation. The study was performed in five elderly, smoking hypertensive patients in whom the clustering of detrimental factors for endothelial function permitted prediction of defective endothelial-mediated vasorelaxation, and five young, normotensive, nonsmoking male volunteers. Forearm blood flow was assessed by venous plethysmography; t-PA and plasminogen activator inhibitor 1 (PAI-1) antigen values were expressed as flow-dependent (net release, the product of venoarterial concentration gradient and forearm blood flow) or independent (absolute and fractional concentration gradients) indices. In patients, acetylcholine did not change flow and net release and concentration gradients of t-PA, suggesting that vasodilatation as such, possibly by increasing fluid shear stress, may induce t-PA release in human forearm. In normal subjects, acetylcholine and sodium nitroprusside increased t-PA antigen net release at the highest infusion rate, an effect attributable to forearm hyperperfusion, since absolute and fractional gradients did not change significantly. PAI-1 antigen did not change during either infusion in both controls and patients, indicating the absence of an endothelial pool to be mobilized acutely.

Drugs by inhalatory route: an overview and upcoming clinical perspectives.

The physical properties of aerosols are reviewed. The physiological basis of inhalation therapy is then briefly reviewed together with the aerosol devices currently available and the therapeutic uses of inhaled drugs, focusing on the treatment of parenchymal lung diseases and extra respiratory disorders. Finally, new perspectives for inhalation therapy are examined.

Aspirin-induced asthma and bronchial hyperresponsiveness.

The inhalation challenge with lysine-aspirin (L-ASA) using the dosimeter method allows the construction of a dose-response curve and the quantitative estimation of airway responsiveness to the drug. We assessed the modifications of airway responsiveness to methacholine in four groups of subjects: aspirin-sensitive asthmatics, aspirin-sensitive subjects with urticaria/angioedema, subjects with an equivocal history of aspirin intolerance and normal control subjects. The L-ASA challenge was positive in all aspirin-sensitive asthmatics. The pattern of bronchial response to the challenge was different from that observed after challenge with allergens or occupational sensitizers. The main difference was found in the recovery from induced bronchoconstriction. The recovery lasted from 3 to 6-8 hours, and a peculiar dose-response curve was obtained that we call "early prolonged reaction". In five of 18 ASA-sensitive subjects there was a significant increase in airway responsiveness. Airway responsiveness was normal in aspirin-sensitive nonasthmatic subjects and in the other two groups studied. We conclude that L-ASA inhalation challenge may increase bronchial hyperresponsiveness in some ASA-sensitive asthmatics. This presence of enhanced bronchial hyperesponsiveness seems to be a marker with which to distinguish ASA-sensitive asthmatics from ASA-sensitive subjects with urticaria/angioedema.

The slide rule: a new method for the assessment of acid-base equilibrium disorders.

AIM: Maps and nomograms are routinely used to evaluate acid-base equilibrium (ABE), but often require previous skilled practice and time to be used in the clinical setting; moreover, some definite alterations may be missed. The aim of this study was to evaluate the new slide rule (patented by Authors) for the rapid, precise and complete assessment and diagnosis of altered blood gas analysis (ABG) parameters and compare it to traditional methods. METHODS: Once pH, bicarbonate and PaCO(2) values are known by arterial blood gas analysis (ABG), the slide rule can calculate, show and instantly diagnose the related alteration, including possible mixed partial compensated ones. In this regard, 330 patients coming from 6 (4 national and 2 foreign) clinics were studied; each patient underwent evaluation of ABG alterations using traditional methods and the slide rule immediately thereafter. RESULTS: The results of consecutive evaluations on involved patients made by specialists in all clinics were in agreement; nonetheless, the slide rule was far more user friendly, rapid and complete in the ABE alterations' diagnostic range, in comparison with traditional methods. CONCLUSION: All involved specialists confirmed that the new slide rule was able to rapidly diagnose ABE alterations, including mixed or partially compensated ones that may be missed by traditional methods.

Amlodipine, enalapril, and dependent leg edema in essential hypertension.

Calcium channel blockers (CCBs) blunt postural skin vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. To evaluate the dose-response relation between this pharmacological interference and dependent edema, a frequent side effect of CCBs during antihypertensive treatment, skin blood flow (laser Doppler flowmetry) at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, and leg weight (Archimedes principle) were measured at baseline, during increasing doses of the dihydropyridine amlodipine (5 and 10 mg UID each for 2 weeks), and after drug withdrawal in 10 hypertensive men. Because angiotensin-converting enzyme inhibitors may attenuate ankle swelling by CCBs, those parameters were evaluated according to a similar design during amlodipine (10 mg UID) and enalapril (20 mg UID) combined (n=10). As a control, the effect of enalapril monotherapy (10 and 20 mg UID for 2 weeks each) was evaluated in a third series of patients (n=8). Amlodipine (5 mg UID) increased leg weight without modifying postural vasoconstriction (the percent skin blood flow decrease from horizontal to dependent position), which indicates that extravascular fluid shift was independent of postural skin vasoconstriction. At 10 mg UID, however, amlodipine blunted postural vasoconstriction and increased leg weight further, which suggests that skin blood flow autoregulation limited additional fluid transfer. Both parameters normalized after drug withdrawal. Enalapril per se did not affect cutaneous vasomotion or leg weight but reduced the amount of dependent fluid extravasation by the CCB despite a persistent antagonism for postural vasoconstrictor responses.

Guillain-Barré syndrome: rehabilitation outcome and recent developments.

Guillain-Barré syndrome is the most common polyneuropathy causing major disability and respiratory failure. Respiratory complications are the main cause of death. Improved respiratory care and new treatment strategies such as plasmaphoresis and immunoglobulin have been shown to improve outcome. We studied the course and outcome of 37 patients with Guillain-Barré syndrome who were admitted to a rehabilitation and respiratory care facility over a 10-year period. There were 21 males and 16 females with a mean age of 62+/-3 years. Fourteen patients developed respiratory failure requiring endotracheal intubation and mechanical ventilation. The mean duration of mechanical ventilation was 38+/-10 days. All patients were successfully liberated from the ventilator. However, 83 percent of the patients were moderately to severely disabled at the time of discharge. Thirteen out of 37 (35 percent) developed long-term disability. None of the patients died over the period of follow-up. These results indicate that early recognition and treatment of respiratory complications in Guillain-Barré syndrome could reduce the morbidity and mortality of this condition.

[Short-term prognosis of pulmonary embolism]. / Prognosi a breve termine dell'embolia polmonare.

Seven hundred fifty four consecutive cases of pulmonary embolism, diagnosed between 1969 and 1982 at S. Chiara Hospital in Pisa, were examined in order to assess the causes and the rate of the early mortality. Full documentation was not obtained in 47 cases (6.2%) and they were excluded from the study; 81 (11.4%) of the remaining 707 died within 30 days of diagnosis, and in 56.8% of them pulmonary embolism was the primary cause of death. The survival rate was 90.6% in patients with apparently primary pulmonary embolism, 89.8% in post surgical cases, 81.5% in cardiac patients and 75% in patients affected by neoplasm. Twenty five per cent of patients were not treated during the acute phase, because the diagnosis was made more than one month after the onset of symptoms or because the fear of bleeding precluded anticoagulant treatment. The incidence of fatal haemorrhage during treatment was 0.5% overall, and 0.4% in surgical patients. Mortality was 9.2% in patients who received treatment, versus 25.2% in untreated patients. Sixteen fatal recurrent embolisms occurred after the end of treatment: 11 were observed in patients not treated with oral anticoagulants. Routine autoptic examinations, performed in 44.4% of the cases, often demonstrated both recent and organized emboli, especially in cardiac patients. Recurrence of pulmonary embolism may account for both the severity of clinical patterns and the high mortality rate in the early phase of treatment.

[Cases of pulmonary embolism diagnosed in Pisa from 1969 to 1984]. / Casi di embolia polmonare diagnosticati a Pisa dal 1969 al 1984.

Starting from 1969, the yearly number of patients with pulmonary embolism documented in the S. Chiara Hospital of Pisa is increased, in spite of the unchanged diagnostic procedures. Aim of this work is to verify if this trend is accompanied by earlier diagnosis with an improvement in the clinical outcome of pulmonary embolism, and if a relevant diagnostic failure is still present in our hospital. A comparison of pulmonary embolism cases collected from 1969 to 1971 and from 1980 to 1982 showed that the number of diagnoses made within one week from the onset of symptoms is increased (+24.8%), whereas the number of diagnoses made after more than one month is reduced (-18.1%). At the same time we observed that cases with a standard PaO2 less than 40 mmHg are reduced (-23.1%) while cases with a standard PaO2 greater than 50 mmHg are increased (+29.9%). An earlier diagnosis of pulmonary embolism contributed to treat a larger percentage of patients (+29.7%) and to lower the early mortality (-17.4%). This diagnostic trend can be ascribed to an increased readiness in raising the clinical suspicion of pulmonary embolism and to the prompt availability of perfusion lung scan, that is the center of our diagnostic strategy. Data of our 1,010 patients, compared with those of autoptic series and with the number of admissions, surgical operations and deaths in the wards of our hospital, suggest some persistent diagnostic failure in patients with well documented embolic risk; such as injured, burned, patients affected by neoplasm or motor lesion, patients operated for orthopedic or gynaecologic problems.

Effect of azelastine on the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. A randomized, double-blind placebo-controlled, crossover study.

Azelastine, a phthalazinone derivative, is a new potent, long acting, orally active anti-allergic compound with particularly strong H1-histamine receptor antagonistic effects which has been proven to possess in vitro and in vivo a number of anti-inflammatory properties. The aim of the present study was to investigate whether azelastine would be able to prevent and/or reverse the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. Twelve atopic patients (5 males, mean age 31 years), skin positive exclusively to grass and/or Parietaria pollen extract, with rhinitis and mild asthma occurring in the spring for at least two years previously, were studied. After a 2 week run-in period, oral azelastine, 4 mg twice daily, or placebo, was given for 2 weeks from the start of the pollen season, according to a randomized, double-blind design. After 2 weeks, the treatments were crossed over. During both the run-in and study periods, patients recorded rhinitis and asthma symptoms, additional antihistamine and bronchodilator drugs taken and peak expiratory flow measurements. A methacholine inhalation test was carried out on four occasions in each patient: before the run-in period, before the start of the treatment, and at the end of the two 2 week treatment periods. Azelastine significantly reduced rhinitis symptoms and the need for antihistamine drugs, whereas asthmatic symptoms, use of bronchodilator drugs, peak flow recordings and bronchial responsiveness to methacholine were unaffected by the treatment. Compliance level and adverse side-effects were not significantly different between active treatment and placebo. In the final subjective evaluation of the two treatments, eight out of 12 patients preferred azelastine.(ABSTRACT TRUNCATED AT 250 WORDS)