Advances on the immunotoxicity of outdoor particulate matter: A focus on physical and chemical properties and respiratory defence mechanisms.

Particulate matter (PM) is acknowledged to have multiple detrimental effects on human health. In this review, we report literature results on the possible link between outdoor PM and health outcomes with a focus on pulmonary infections and the mechanisms responsible for observed negative effects. PM physical and chemical properties, such as size and chemical composition, as well as major emission sources are described for a more comprehensive view about the role played by atmospheric PM in the observed adverse health effects; to this aim, major processes leading to the deposition of PM in the respiratory tract and how this can pave the way to the onset of pathologies are also presented. From the literature works here reviewed, two ways in which PM can threaten human health promoting respiratory infectious diseases are mostly taken into account. The first pathway is related to an enhanced susceptibility and here we will also report on molecular mechanisms in the lung immune system responsible for the augmented susceptibility to pathogens, such as the damage of mechanical defensive barriers, the alteration of the innate immune response, and the generation of oxidative stress. The second one deals with the relationship between infectious agents and PM; here we recall that viruses and bacteria (BioPM) are themselves part of atmospheric PM and are collected during sampling together with particles of different origin; so, data should be analysed with caution in order to avoid any false cause-effect relation. To face these issues a multidisciplinary approach is mandatory as also evident from the ongoing research about the mechanisms hypothesized for the SARS-CoV-2 airborne spreading, which is still controversial and claims for further investigation. Therefore, we preferred not to include papers dealing with SARS-CoV-2.

[Posterior echocardiography windows: usefulness in clinical practice]. / Le finestre ecocardiografiche posteriori: utilità nella pratica clinica.

Posterior cardiac structures cannot always be imaged by means of standard transthoracic echocardiography. Left pleural effusion leading to pulmonary atelectasis and/or to displacement of air-filled pulmonary tissue displacement, allows ultrasound transmission from a patient's back to his heart through a liquid interface. In this study we present the clinical usefulness of echocardiographic posterior windows for the diagnosis of constrictive pericarditis and aortic dissection in 2 patients in whom the standard transthoracic approach did not permit diagnostic imaging. We conclude that, in the case of left pleural effusion, the use of posterior windows should be encouraged.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

Angiotensin-converting enzyme inhibition facilitates alveolar-capillary gas transfer and improves ventilation-perfusion coupling in patients with left ventricular dysfunction.

OBJECTIVE: The backward effects of left ventricular dysfunction include alterations in alveolar-capillary gas transfer and ventilation-perfusion coupling. Because the angiotensin-converting enzyme (ACE) is highly concentrated in the vascular endothelium of the lungs, we examined whether ACE inhibitors may influence the pulmonary function in patients with congestive heart failure. METHODS: In 20 patients with idiopathic cardiomyopathy, pulmonary function and exercise capacity were evaluated at baseline and 6 and 12 months after treatment with enalapril (10 mg twice a day) was started. The study also included 19 age- and sex-matched control subjects with mild primary hypertension and normal left ventricular function who were given enalapril as a standard treatment of high blood pressure. RESULTS: In congestive heart failure, forced expiratory volume in 1 second, vital capacity, and total lung capacity did not vary significantly with enalapril; alveolar-capillary diffusion of carbon monoxide (DL(CO)) increased toward normal; exercise tolerance time, peak exercise oxygen uptake (peak VO2), minute ventilation and tidal volume (peak VT) also increased; and the ratio of volume of dead space (VD) to VT (peak VD/VT) at peak exercise reduced. Changes in peak VO2 showed a direct correlation with those in DL(CO) and an inverse correlation with those in peak VD/VT. Results at 6 and 12 months were comparable. Enalapril did not affect these variables in the control population. CONCLUSIONS: In patients with idiopathic cardiomyopathy heart failure, but not in control subjects, gas transfer and ventilation-perfusion improved with ACE inhibition. These pulmonary changes may contribute to the associated increase in exercise tolerance.

Oxygen consumption.

It gets more and more frequent to use oxygen consumption (VO2) to evaluate exercise capacity and response to treatment in heart failure patients. The amount of VO2 is due to ventilation, oxygen transport and muscle activity. No one of these single steps can define by itself VO2, but all these physiological functions are integrated each other. In this paper we examine the modifications of cardiac output, arteriovenous oxygen content difference, and the temporal behavior of their variations during exercise in heart failure. We specifically describe changes in VO2 during simulated altitude; we also contemplate mechanisms governing oxygen diffusion from capillary bed to mitochondria and critical capillary PO2 concept.

[Effectiveness of long-term ACE-inhibition on pulmonary diffusion and ventilation-perfusion ratio in chronic heart failure: correlation with physical performance]. / Efficacia a lungo termine dell'ACE-inibizione su diffusione polmonare e accoppiamento ventilazione-perfusione nell'insufficienza cardiaca cronica: relazione con la performance fisica.

Pulmonary dysfunction contributes to exercise intolerance in patients with chronic heart failure, and ACE-inhibition improves the functional capacity of these subjects. In this study, we investigated whether and how ACE-inhibitors affect pulmonary function and ventilatory response during exercise in chronic heart failure. Twenty patients with idiopathic dilated cardiomyopathy and left ventricular ejection fraction < 35% underwent pulmonary function tests and exercise evaluation with analysis of expired gases before and after 1 year of treatment with enalapril (10 mg bid). To explore whether or not the respiratory influence of ACE-inhibitors is peculiar to the syndrome of cardiac failure, we also studied 19 subjects with mild, untreated primary hypertension who followed the same protocol. In this group, enalapril exerted a neutral effect on pulmonary function. In chronic heart failure patients, lung volumes were abnormal and did not improve after enalapril treatment; on the contrary, alveolar diffusing capacity for carbon monoxide increased towards normal values. Exercise tolerance time, peak exercise oxygen consumption, ventilation, and tidal volume also improved and the dead space to tidal volume ratio was reduced at the peak exercise and intermediate exercise phases (20, 60 W). Changes in carbon monoxide diffusion were positively correlated to those occurring during peak exercise oxygen consumption. A negative correlation was found between the variations in oxygen consumption and those in dead space to tidal volume ratio at peak exercise. We conclude that in patients with chronic heart failure, ACE-inhibition restores diffusing lung properties and improves ventilation-perfusion matching during exercise. In this syndrome, sustained reduction in gas exchange resistance is a fundamental therapeutic property of this class of drugs.

Comparison of changes in respiratory function and exercise oxygen uptake with losartan versus enalapril in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.

[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity]. / Antagonismo di acido acetilsalicilico vs ACE-inibitore nell'insufficienza cardiaca congestizia rivelato da una diminuita capacità respiratoria e di esercizio.

Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.

[Food intolerance and irritable bowel syndrome of childhood: clinical efficacy of oral sodium cromoglycate and elimination diet]. / Intolleranza alimentare e sindrome dell'intestino irritabile del bambino: efficacia terapeutica del sodiocromoglicato orale e della dieta di esclusione.

Irritable bowel syndrome (IBS) is recognized to be a common cause of chronic diarrhea without failure to thrive in childhood. Several studies stressed the role of food intolerance as a major factor in the pathogenesis of IBS. The aim of this multicenter study was to investigate the offending role of food in IBS and to compare the therapeutic role of oral sodium cromoglycate versus elimination diet. 153 patients (mean age 4 years) with diarrhea (> 3 stools per day for four days in a week) and abdominal pain for about 10 months were enrolled in this trial. About half of the patients had a family history positive for atopy and 70% of the cases complained of intestinal symptoms after food ingestion. In 17% of the patients Skin Prick test (SPT) resulted positive to at least one food allergen and 87% of positive reactions to SPT was provoked by common foodstuffs. 87% of patients treated with elimination diet (rice, lamb, turkey, lettuce, carrots, sweet potatoes, pears, oil, tea, salt, mineral water, brown sugar) and 97% of patients treated with SCG (mean 63 mg/kg/day) for one month showed a significant improvement of intestinal symptoms. An elimination diet for several weeks can produce, beside a bad compliance (23% of patients admitted to our study didn't strictly follow diet regimen) also a nutritional deprivation. The results of this trial suggest that it's correct to investigate the role of food in children with diarrhea not due to organic diseases and diagnosed such as IBS and to use oral SCG to obtain the improvement of these symptoms.