Accuracy of positive airway pressure titration through telemonitoring of auto-adjusting positive airway pressure device connected to a pulse oximetry in patients with obstructive sleep apnea.

PURPOSE: In COVID-19 era, all forms of access of patients to the sleep units should be reduced as much as possible when implementing telemedicine. In the field of obstructive sleep apnea (OSA) therapy with positive airway pressure (PAP) devices, telemedicine includes the use of built-in software (BIS) and storage of PAPs and remote-controlled data (BISrc data) that are processed and transmitted daily to sleep units. We compared two methods of evaluating the final residual severity of OSA patients in home PAP titration: BISrc data versus nocturnal portable multichannel monitoring (PM) data in PAP (reference method) and to verify whether the efficacy PAP therapy guided by BISrc data was clinically adequate. METHODS: We conducted a real-life prospective study in newly diagnosed patients with OSA. Patients used an auto-adjusting positive airway pressure (AirSense 10 ResMed) with a pulse oximeter that allows daily transfer of BISrc data (apnea hypopnea index [AHI] and SaO2 ) and remote changes in ventilator setting. Once the PAP titration was completed, the pressure value or ranges were kept constant for 3 days and home PM was repeated. RESULTS: There were 41 patients with moderate to severe OSA who completed the study. When considering AHI only, the diagnostic accuracy of BISrc on the third day was equal to 97.5%; when considering AHI > 10/h, ODI > 10/h, and SaO2 < 90%, the diagnostic accuracy slightly decreased to 90.2%. CONCLUSION: In clinical practice, the two measurement methods are equivalent. The use of BISrc data for home titration would reduce the access to sleep units. We urge that widespread use of BISrc be promoted in the current practice of management of OSA.

Is the use of beta-blockers in COPD still an unresolved dilemma?

Beta-blockers are competitive antagonists at beta-adrenergic receptors (beta-AR) and are a life-saving form of treatment in different cardiovascular diseases (CVD). Despite current guidelines supporting the use of selective beta(1)-blockers in patients with CVD and especially in heart failure (HF), they are still largely underused, mostly as a consequence of the presence of chronic obstructive pulmonary disease (COPD). In primary care, prevalence of COPD in patients with HF is approximately 25%, and it will rise in the next years. In the general population, only 20% of COPD patients with HF are treated with beta-blockers. beta-Blockers may result in pulmonary adverse effects that are relevant to COPD patients. Bronchoconstriction may be the consequence of: absence of cardioselectivity; loss of cardioselectivity at high doses, and unopposed stimulation of cholinergic muscarinic M(2) receptors. The concern of inducing bronchospasm is the more likely explanation of a poor prescription of beta-blockers in patients with CVD also suffering from COPD. However, under carefully controlled conditions, which include close monitoring of lung function and appropriate selection of the drug and titration of the dose on a case-by-case basis, selective beta(1)-blockers can be safely administered to most patients with COPD. Pneumologists and cardiologists should develop a detailed and standardized protocol to guide the use of selective beta(1)-blockers in everyday practice, which could significantly reduce the physicians' mistrust of beta-blockers in COPD patients.

Alveolar-derived exhaled nitric oxide is reduced in obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular diseases, in particular systemic arterial hypertension. We postulated that intermittent nocturnal hypoxia in OSAS may be associated to decreased fractional exhaled nitric oxide (FENO) levels from distal airspaces. METHODS: Multiple flow rate measurements have been used to fractionate nitric oxide (NO) from alveolar and bronchial sources in 34 patients with OSAS, in 29 healthy control subjects, and in 8 hypertensive non-OSAS patients. The effect of 2 days of treatment with nasal continuous positive airway pressure (nCPAP) on FENO was examined in 18 patients with severe OSAS. RESULTS: We found that the mean [+/- SE] concentrations of exhaled NO at a rate of 50 mL/s was 21.8 +/- 1.9 parts per billion (ppb) in patients with OSAS, 25.1 +/- 3.3 ppb in healthy control subjects, and 15.4 +/- 1.7 ppb in hypertensive control patients. The mean fractional alveolar NO concentration (CANO) in OSAS patients was significantly lower than that in control subjects (2.96 +/- 0.48 vs 5.35 +/- 0.83 ppb, respectively; p < 0.05). In addition, CANO values were significantly lower in OSAS patients with systemic hypertension compared to those in normotensive OSAS patients and hypertensive patients without OSAS. The mean values of CANO significantly improved after nCPAP therapy (2.67 +/- 0.41 to 4.69 +/- 0.74 nL/L, respectively; p = 0.01). CONCLUSIONS: These findings suggest that alveolar FENO, and not bronchial FENO, is impaired in patients with OSAS and that this impairment is associated with an increased risk of hypertension. NO production within the alveolar space is modified by treatment with nCPAP.

Step-down compared to fixed-dose treatment with inhaled fluticasone propionate in asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) are an effective treatment of asthma even when administered at a low dose. Once asthma is controlled, current guidelines recommend that the dose of ICS be reduced to the lowest possible and effective dose. Although the most appropriate strategy for the stepping down has not yet been defined, quantification of sputum eosinophils and bronchial hyperresponsiveness (BHR) are indeed measures of asthma control. OBJECTIVE: To compare the efficacy of step-down and fixed-dose strategies in the control of BHR to methacholine and eosinophilic inflammation patients with mild-to-moderate asthma. METHODS: We performed a double-blind, randomized study to compare inhaled fluticasone propionate (FP), 1,000 microg/d, then reduced to 200 microg/d (group 1; n = 18) to a fixed dose of FP, 200 microg/d (group 2; n = 17) administered for 6 weeks and then 8 weeks in reducing the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and sputum eosinophils in 35 patients. The duration of the efficacy was also followed subsequently after 8 weeks of placebo treatment. RESULTS: PD20 remarkably increased with both treatment strategies, but differences between groups were not significant. Sputum eosinophils (median values, percentage) at baseline and after each treatment period were not different (group 1, 16.4 to 1.0 to 2.7%; group 2, 16.7 to 2.8 to 2.8%, respectively). The percentages of patients in whom sputum eosinophilia was normalized (< or = 3%) were as follows: group 1, 69% and 60%; group 2, 50% and 57%. After placebo treatment, sputum eosinophils were still "normalized" in approximately one third of patients. CONCLUSION: Step-down and fixed-dose strategies with FP improved PD20 and sputum eosinophilia to a similar degree. The effect on sputum eosinophils persisted longer than that on methacholine.

[Inhaled corticosteroid therapy in adults with asthma. Current evidences]. / Attuali concetti sull'uso dei corticosteroidi per via inalatoria nella terapia dell'asma dell'adulto.

Different international guidelines recommend the early introduction of inhaled corticosteroids (ICS) and their regular use to gain clinical and functional control of persistent asthma. There is now evidence that the starting dose of all ICS is lower than previously regarded. Initial moderate ICS doses appear to be more effective than an initial low ICS dose. The lowest effective dose should always be seeked by a step-down procedure. More than 90% of benefit is achieved by approximately a daily regular dose of 200 microg of fluticasone or 400 microg of beclomethasone or budesonide. The beneficial effects of increasing the dose of ICS alone appear to be modest in most cases. Intermittent ICS therapy has been successfully used in the long term treatment of mild asthma. In general, twice-daily administration of ICS provides greater therapeutic benefit than a once-daily regimen in moderate asthma. When asthma control has been obtained, a once-daily regimen can be tried. In clinical practice, this has the potential advantage of increasing patients' compliance. Chlorofluorocarbon-free formulations of old ICS have also remarkably improved their clinical efficacy mainly through an increased peripheral deposition pattern. Despite some limitations due to poor response in neutrophilic asthma and to potential systemic side effects, ICS will certainly be the cornerstone of asthma therapy even the next future.

Effect of heliox breathing on dynamic hyperinflation in COPD patients.

BACKGROUND: and objective: Patients with COPD exhibit increased inspiratory work and dyspnea due to dynamic hyperinflation caused by expiratory flow limitation. Helium-oxygen mixtures (ie, heliox) have been used in treating these patients on the assumption that, by lowering airway resistance, they might be beneficial. METHODS: In 22 patients with COPD, the presence of expiratory flow limitation was assessed with patients in the sitting and supine positions using the negative expiratory pressure technique, and the effects of heliox (80% He, 20% O2) on breathing pattern, expiratory flow limitation, and dynamic hyperinflation, evaluated from the change in inspiratory capacity (IC), were measured at rest and were compared with those due to inhaled salbutamol. RESULTS: During air breathing, 13 patients experienced flow limitation while in the sitting position and 18 experienced flow limitation while in the supine position. Neither heliox nor salbutamol therapy changed the breathing pattern in any of the patients, regardless of posture and the presence or absence of expiratory flow limitation. However, in both positions IC increased significantly in most flow-limited patients after bronchodilator administration, but not after heliox administration. CONCLUSIONS: Since heliox had no effect on dynamic hyperinflation, the use of this gas mixture, which is costly and cumbersome, does not appear to be beneficial in stable patients with COPD breathing at rest.

Induced sputum and bronchoalveolar lavage from patients with hypersensitivity pneumonitis.

BACKGROUND AND AIM: Hypersensitivity pneumonitis (HP) is an immunologically induced inflammation of the lung parenchyma, though bronchial airways may be also involved. The aim of this study was to compare the cellular profiles of induced sputum (IS) in patients with newly diagnosed HP to that of healthy subjects, and to examine the relationship between inflammatory cells from IS and BAL. METHODS: Nine HP patients and 9 healthy volunteers were studied. IS was obtained by inhalation of hypertonic saline solution in all subjects. Bronchoscopy was performed on a different occasion in all patients and in five controls. RESULTS: IS was well tolerated and preferred to BAL by all subjects. Both IS and BAL from HP patients showed a significant increase in total cells (P < 0.02 and P < 0.001) and in lymphocytes (P < 0.02 and P < 0.001) and a significant decrease in macrophages (P < 0.05 and P < 0.001), when compared with normal subjects. In HP patients, total cells number in IS was higher than that in BAL (P < 0.02). Moreover, the percentage of lymphocytes was significantly lower in IS than in BAL (P < 0.001). No significant relationship was found between total cells or inflammatory cells from IS and the corresponding ones from BAL and wide limits of agreement were found between lymphocytes from IS and BAL. CONCLUSIONS: This study demonstrated that both BAL and IS from newly diagnosed HP patients contained significantly more total cells and lymphocytes, when compared to healthy subjects. Moreover, differential cell counts in HP patients showed that IS and BAL reflected different compartments of inflammation. Thus, IS could represent a complementary, but not alternative tool to bronchoscopy both in research and in the clinical monitoring of HP patients.

Cardiorespiratory response to walk in multiple sclerosis patients.

To ascertain whether fatigue perception is linked to exertion dyspnea and/or to an impaired cardiorespiratory response during walk, 11 patients (8 females, age range 21-46 years) with multiple sclerosis (MS) and mild disability underwent the 6-min walk test. Ten healthy subjects (7 females, age range 25-49 years) were studied, as a control group. Patients did not differ from controls in spirometry, lung volumes and respiratory muscle strength. There was a significant difference in walk distance between patients and controls (P<0.001), but not in dyspnea perception. In patients, the walk distance significantly related to disability score (P<0.01), but not to fatigue. Compared to controls, patients had a significant decrease in oxygen pulse during walk (P<0.05) and a significant increase in the ventilatory equivalent of CO2 both at baseline and during walk (P<0.05). The relative contribution of both the tidal volume and of the ratio of inspiratory to total breathing cycle duration to the increase in minute ventilation during walk was significantly less in patients, as compared to controls (P<0.05). We conclude that in MS patients with mild disability, fatigue and exertion dyspnea are different sensations without any link and a peripheral limitation during walk can occur.

Acute effects of indacaterol on lung hyperinflation in moderate COPD: a comparison with tiotropium.

BACKGROUND: Evidence has been provided that high-dose indacaterol (300 µg) can reduce lung hyperinflation in moderate-to-severe chronic obstructive pulmonary disease (COPD). AIM: To study whether low-dose indacaterol (150 µg) also reduces lung hyperinflation in comparison with the recommended dose of tiotropium (18 µg) in moderate COPD. METHODS: This was a multicenter, randomized, blinded, 3-period cross-over, placebo-controlled study. Spirometry and lung volumes were measured before and 30, 60, 120, 180 and 240 min after the administration of single-doses of indacaterol, tiotropium, or placebo. The primary end-point was the change in peak inspiratory capacity (IC). The area under the 4-h curve (AUC(0-4)) for IC, 1-s forced expiratory volume (FEV(1)) and forced vital capacity (FVC) were secondary variables. RESULTS: 49 patients completed the study. On average, peak IC and AUC(0-4) for IC were significantly greater after indacaterol than placebo by 177 mL (p = 0.007) and 142 mL (p = 0.001), respectively. Differences in peak IC and AUC(0-4) for IC between tiotropium and placebo were 120 mL (p = 0.07) and 85 mL (p = 0.052), respectively. Differences between indacaterol and tiotropium were statistically insignificant. Peak IC increased by >20% in 12 patients with indacaterol and 9 with tiotropium (p = 0.001), and by >30% in 8 patients with indacaterol and 3 with tiotropium (p = 0.001). The effects of indacaterol and tiotropium on FEV(1) and FVC were statistically significant vs placebo. CONCLUSIONS: Low-dose indacaterol has a bronchodilator effect that is similar to the recommended dose of tiotropium, but it is slightly superior in reducing lung hyperinflation. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00999908.

Clinical and functional prediction of moderate to severe obstructive sleep apnoea.

INTRODUCTION: Upper airway inflammation and narrowing are characteristics of obstructive sleep apnoea (OSA). Inflammatory markers have been found to be increased in exhaled breath and induced sputum of patients with OSA. OBJECTIVES: The aim of this study was to investigate if the measurement of exhaled nitric oxide (F(ENO) ), as marker of airway inflammation, together with the forced mid-expiratory/mid-inspiratory airflow ratio (FEF(50) /FIF(50) ), as marker of upper airway narrowing, may help to predict OSA. METHODS: Two hundred one consecutive outpatients with suspected OSA were prospectively studied between January 2004 and December 2005. All patients underwent clinical examination, spirometry with measurement of FEF(50) /FIF(50) , maximum inspiratory pressure, arterial blood gas analysis, exhaled nitric oxide (F(ENO) ) and overnight polysomnography. Linear regression models were used to evaluate the effect of measured variables on the apnoea-hypopnoea index (AHI). Models were cross-validated by bootstrapping. RESULTS: Most of the patients were obese and had severe OSA. FEF(50) /FIF(50) , F(ENO) and an interaction term between smoking and F(ENO) contributed significantly to the predictive model for AHI, in addition to age, neck circumference, body mass index and carboxyhaemoglobin saturation. A nomogram to predict AHI was obtained, which converted the effect of each covariate in the model to a 0-100 scale. The nomogram showed a good predictive ability for AHI values between 25 and 64. CONCLUSIONS: The measurement of F(ENO) and of FEF(50) /FIF(50) improves the ability to predict OSA and may be used to identify patients who require a sleep study.

Psychological implications of respiratory health and disease.

The possibility that a subject's psychological status may influence respiratory sensations and that chronic respiratory disease may have psychological consequences has sparked great interest among clinicians and researchers. This paper reviews the existing research on the association between respiratory symptom perception and the psychological status and between chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease, and psychological disturbances. Moreover, it focuses on the role of stressful events in determining asthma exacerbations. The recent literature suggests that in patients with chronic respiratory diseases, the evaluation of breathlessness perception, psychological disturbances and the recording of any stressful events should be considered as relevant as the physical and functional assessment of respiration.

Inhaled corticosteroids and leukotriene modifiers in the acute treatment of asthma exacerbations.

Asthma exacerbation has a considerable impact on patients' quality of life and constitutes a challenging condition for primary health-care providers. Severe exacerbations are also an important cause of hospital admissions and require high costs. Despite this, a widely accepted definition is still lacking; etiologic and pathogenetic mechanisms are still incompletely defined. Although the efficacy of inhaled corticosteroids (ICS) and leukotriene modifiers in preventing mild to moderate asthma exacerbation is well recognized, their role within the context of an asthma action plan in general practice and in home-based early intervention for acute exacerbations is still controversial. Although systemic corticosteroids (CS) are standard care for severe exacerbation in the emergency department's (ED) management of asthma, published evidence suggests that high doses of ICS may be beneficial in the ED. The additive benefit of ICS when used with systemic CS is still debated. Data on leukotriene modifiers in the management of asthma exacerbation are limited. However, therapeutic strategies of this emergency including ICS and leukotriene modifiers seem logical and may be suitable, at least in certain patient groups. The availability of different drugs, active on different targets, can potentially contribute to a better management of asthma exacerbations.

Assessment of breathlessness perception by Borg scale in asthmatic patients: reproducibility and applicability to different stimuli.

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from -2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patient's breathlessness perception by this technique in clinical settings and in the physiology laboratory.

Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone.

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.