The mechanics of the lung parenchyma and airway responsiveness to metacholine.

The lung parenchyma is anatomically and mechanically connected to the intraparenchymal airways. Due to forces of interdependence the lung parenchyma represents a mechanical load that opposes bronchial narrowing during airway smooth muscle activation. The mechanical load caused by the parenchyma is a function of the number of the alveolar attachments to the airways, and of the mechanical properties of the parenchyma. The extracellular matrix is a major component of the lung parenchyma responsible of most of its mechanical properties. The excessive airway narrowing observed in the asthmatic population may be the consequence of the altered mechanical properties of the extracellular matrix reducing the mechanical load that opposes airway smooth muscle contraction

Airways oxidative stress, lung function and cognitive impairment in aging.

Abstract BACKGROUND: An altered balance of oxidants/antioxidants is one of the pathological mechanisms of many age-dependent disorders. We aimed to investigate the age-related airways oxidative stress, using non invasive, safe and repeatable techniques; to evaluate the correspondence between systemic and local oxidative stress in healthy subjects of different age ranges; to analyse the correlation between systemic and local oxidative stress with lung function and with cognitive impairment. METHODS: Thirty consecutive healthy high school graduated subjects (8 M, 22 F), divided in three ranges of age ( 60 years) were enrolled. All subjects underwent oxygen free radicals and exhaled nitric oxide measurement (by the diacron reactive oxygen metabolites test and by a rapid-response chemiluminescence nitric oxide analyzer), lung function tests, and cognitive impairment scales (Mini Mental State Examination and Geriatric Depression Scale). RESULTS: A significant increase of oxygen free radicals, exhaled nitric oxide, and Geriatric Depression Scale score and a significant decrease of forced expiratory volume in 1 second and forced expiratory vital capacity from younger to older subjects were identified. Moreover, the significant positive correlation between oxygen free radicals and exhaled nitric oxide, and between oxygen free radicals and exhaled nitric oxide with Geriatric Depression Scale score were found. The significant negative correlation between forced expiratory volume in 1 second and oxygen free radicals or exhaled nitric oxide was also demonstrated. CONCLUSIONS: Our data supports the role of progressive local oxidative stress in damaging the lung function and in inducing depression symptoms

Long term evaluation of mental fatigue by Maastricht Questionnaire in patients with OSAS treated with CPAP

Background. Patients with obstructive sleep apnoea syndrome (OSAS) suffer from disrupted sleep. Impaired nightly sleep leads to increase physical and mental fatigue. The effect of long term continuous positive airway pressure (CPAP) on mental fatigue in OSAS patients, assessed by Maastricht Questionnaire (MQ), has not been investigated yet. Methods. In order to evaluate the role of CPAP in improving mental fatigue of patients with OSAS, we studied 35 patients (26 males, age <65 years at the time of the diagnosis) affected by OSAS, established by polysomnography (PSG). Patients were divided into two groups; 19 subjects (15 males), who refused CPAP therapy, and 16 patients (11 males) well matched for sex, age, body mass index (BMI), neck circumference, duration of follow up, and severity of disease, who had been treated with CPAP for at least two years. Results. All patients had severe OSAS with Respiratory Disturbance Index (RDI), of 48±20.9 (range 22-90) and 61.48±18.6 (range 34-101) respectively, for group one (untreated patients) and group two (CPAP treatment). In addition, all patients had severe impairment of mental fatigue and of daytime sleepiness, demonstrated by high values of MQ score (32.17±15.33 and 37.36±12.4, respectively) and Epworth Sleepiness Scale (ESS) (14.21±4.77 and 15.06±6.07 respectively). There was no statistical significant difference in the group one at baseline and after follow- up, in terms of BMI, MQ score, ESS, and RDI. In the CPAP group (group two), the patients reported a significant improvement of the quality of their mental health (MQ 37.36±12.4 vs. 16.41±9.02; p<0.0001) and sleepiness (ESS 15.06±6.07 vs. 4.13±3.93; p<0.0001) with a stable BMI. There was significant correlation between the severity of sleep apnoea, expressed as RDI, and MQ at admission compared to at the end of follow-up (r=0.4, p<0.05). Conclusions. This study demonstrates an evident deterioration of mental fatigue in patients with OSAS, directly correlated to the severity of nocturnal disorder breathing; however supports the hypothesis that long term CPAP therapy significantly improves sleepiness and mental fatigue

Cold exposure affects carbohydrates and lipid metabolism, and induces Hog1p phosphorylation in Dekkera bruxellensis strain CBS 2499

Dekkera bruxellensis is a yeast known to affect the quality of wine and beer. This species, due to its high ethanol and acid tolerance, has been reported also to compete with Saccharomyces cerevisiae in distilleries producing fuel ethanol. In order to understand how this species responds when exposed to low temperatures, some mechanisms like synthesis and accumulation of intracellular metabolites, changes in lipid composition and activation of the HOG-MAPK pathway were investigated in the genome sequenced strain CBS 2499. We show that cold stress caused intracellular accumulation of glycogen, but did not induce accumulation of trehalose and glycerol. The cellular fatty acid composition changed after the temperature downshift, and a significant increase of palmitoleic acid was observed. RT-PCR analysis revealed that OLE1 encoding for \u3949-fatty acid desaturase was up-regulated, whereas TPS1 and INO1 didn't show changes in their expression. In D. bruxellensis Hog1p was activated by phosphorylation, as described in S. cerevisiae, highlighting a conserved role of the HOG-MAP kinase signaling pathway in cold stress response

Changes in sputum composition during 15min of sputum induction in healthy subjects and patients with asthma and chronic obstructive pulmonary disease

SummaryIntroductionThe use of sputum induction by inhalation of hypertonic saline to study the cellular and biochemical composition of the airways allows noninvasive sampling of the airways content and identification of markers of airways inflammation.ObjectiveThe present study aimed to identify possible changes in the cellular composition of induced sputum between samples obtained sequentially (three periods of 5min each) during one sputum induction. Moreover, difference between these samples and the mixed one (mixture of samples obtained after 5, 10 and 15min of induction) was investigated.MethodsForty-six subjects (10 healthy volunteers, 12 patients with chronic obstructive pulmonary disease (COPD) and 24 patients with asthma) (mean age 53.0±14.0yr, forced expiratory volume in one second (FEV1) 71.8±19.0% pred) produced sputum after three consecutive 5min periods of hypertonic (4.5%) saline inhalation. Stained cytospins from the three periods separately and from the mixed sample were produced and analyzed.ResultsThe mean percentage of neutrophils, eosinophils, lymphocytes and epithelial cells did not change significantly in samples obtained consecutively after 5, 10 and 15min of the induction procedure. There was no significant difference in the cellular composition of samples obtained after 5, 10 and 15min of induction and the cellular composition of the mixed sample (P=0.06).ConclusionThe separate analysis of induced sputum from three consecutive sampling and the mixed sample did not demonstrate significant changes in their cellular composition. Fifteen minutes induction procedure with the fixed concentration of hypertonic saline and processing of the mixed sample can be recommended for clinical settings and clinical trials

SARS-CoV-2 serological profile in healthcare professionals of a Southern Italy hospital

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of “Policlinico Riuniti”, Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG—positive tests; 62 (1.9%; 95% CI: 1.4–2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5–2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5–2.5). Overall, within eight weeks, we detected a mean reduction of –17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia’s hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections

Assessment of tryptophan, tryptophan ethylester, and melatonin derivatives in red wine by SPE-HPLC-FL and SPE-HPLC-MS methods

Melatonin (MEL) is an indoleamine produced mainly by the pineal gland in vertebrates. It plays a significant role in the regulation of circadian rhythms, mitigation of sleeping disorders, and jet lag. This compound is synthetized from tryptophan (TRP) and it has been found in seeds, fruits, and fermented beverages, including wine. Wine is also a source of other tryptophan derivatives, the tryptophan ethylester (TEE) and MEL isomers (MISs), for which the biological properties need to be elucidated. An analytical method for the simultaneous quantification of TRP, TEE, and MEL was developed by a Solid Phase Extraction (SPE) of a preconcentration of wine followed by high performance liquid chromatography (HPLC) analysis either with fluorescence or mass spectrometer detectors. The analytical method showed a relative standard deviation (RSD) lower than 8%, except for TRP (RSD 10.5% in wine). The recovery was higher than 76%. The versatility of SPE preconcentrations allowed for the adequate preconcentration of wine sample as well as detection of low concentrations, an important aspect especially for MEL (detection limit 0.0023 \ub5g/L). The proposed method proved to be suitable for assessing the investigated compounds in some red wine samples, where 74.4-256.2 \ub5g/L and 0.038-0.063 \ub5g/L of TEE and MEL were detected, respectively. Five MISs were also found in wine samples in concentrations up to 1.97 \ub5g/L

Increased IL-6 and IL-4 in exhaled breath condensate of patients with nasal polyposis

Background and Aim. Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome.The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. Methods. Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. Results. Concentrations of oral and nasal exhaled IL- 6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p<0.001) and IL-4 (p<0.05) was observed after polypectomy. Conclusions. We consider oral and nasal exhaled condensate of IL-6 and IL-4 as valid inflammatory and oxidative stress marker in patients with nasal polyposis

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI)

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics

COVID-19 in Severe Asthma Network in Italy (SANI) patients: Clinical features, impact of comorbidities and treatments

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