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ObjectivesCOVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients’ outcomes is still poorly understood.DesignObservational, prospective, multicentre study.SettingThree academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards.ParticipantsConsecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded.InterventionsAnthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101–200 mm Hg); mild (PaO2/FiO2 201–300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg).Primary and secondary outcome measuresThe primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay.Results412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55–76) years with a PaO2/FiO2 at admission of 262 (140–343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04).ConclusionsA moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality.Trial registration numberNCT04307459

Background Epidemiology of dysphagia and its drivers in obstructive sleep apnea (OSA) are poorly understood. The study aims to investigate the prevalence of dysphagia symptoms and their association with demographic and clinical factors in patients with OSA. Methods Patients with OSA referring to an Academic Sleep Outpatient Clinic were enrolled in a prospective study. Demographic, clinical characteristics, and OSA symptoms were collected. All patients underwent home sleep cardiorespiratory polygraphy and the Eating-Assessment Tool questionnaire (EAT-10) to investigate dysphagia symptoms. Patients with a positive EAT-10 were offered to undergo a fiberoptic endoscopic evaluation of swallowing (FEES) to confirm the presence of dysphagia. FEES findings were compared with a healthy control group. Univariate and multivariate analyses were performed to assess predictors of dysphagia. Results 951 patients with OSA (70% males, age 62 IQR51-71) completed the EAT-10, and 141 (15%) reported symptoms of dysphagia. Female gender (OR = 2.31), excessive daily sleepiness (OR = 2.24), number of OSA symptoms (OR = 1.25), anxiety/depression (OR = 1.89), and symptoms of gastroesophageal reflux (OR = 2.75) were significantly (p < 0.05) associated with dysphagia symptoms. Dysphagia was confirmed in 34 out of 35 symptomatic patients that accepted to undergo FEES. Patients with OSA exhibited lower bolus location at swallow onset, greater pharyngeal residue, and higher frequency and severity of penetration and aspiration events than healthy subjects (p < 0.05). Conclusion A consistent number of patients with OSA show symptoms of dysphagia, which are increased in females and patients with a greater OSA symptomatology, anxiety and depression, and gastroesophageal reflux. The EAT-10 appears a useful tool to guide the selection of patients at high risk of dysphagia. In clinical practice, the integration of screening for dysphagia in patients with OSA appears advisable.

BackgroundPsoriatic arthritis (PsA) patients are often affected by numerous comorbidities. However, contrasting results have been reported with regard to the respiratory involvement in PsA patients. The aim of this study was to evaluate the presence of subclinical airway inflammation in non-smoking PsA patients compared to patients with only psoriasis using the fraction of exhaled nitric oxide (FeNO) as an indirect marker of airway inflammation.MethodsThe study included 164 non-smoking psoriatic patients (Psoriasis Area of Severity Index or PASI score > 10): 82 with and 82 without PsA, who underwent FeNO tests at different flow rates (30, 50, 100, 200 mL/s). PsA patients were evaluated with Disease Activity in PSoriatic Arthritis Score (DAPSA). Both study groups were compared in terms of FeNO values and its association with the PASI score. The correlations between the variables were evaluated by means of Pearson’s coefficient.ResultsPatient with PsA had higher levels of FeNO than those with psoriasis but without arthritis (at 30 mL/s, 71.09 ± 18.40 ppb vs 66.88 ± 19.12 ppb (NS); at 50 mL/s, 36.61 ± 9.30 ppb vs 30.88 ± 9.73 ppb (p < 0.001); at 100 mL/s, 19.09 ± 4.66 ppb vs 16.63 ± 4.90 ppb (p < 0.001); and at 200 mL/s, 10.88 ± 2.53 ppb vs 9.43 ± 2.55 ppb (p < 0.001), respectively). PASI score correlated to FeNO only in psoriatic patients without arthritis. However, CASPAR index correlated with FeNO (FeNO30: r = 0.81, p < 0.001; FeNO50: r = 0.84, p < 0.001; FeNO100: r = 0.71, p < 0.001; FeNO200: r = 0.58, p < 0.001). DAPSA was also correlated with FeNO to all flows (FeNO30: r = 0.43, p < 0.001; FeNO50: r = 0.33, p < 0.001; FeNO100: r = 0.34, p < 0.001; FeNO200: r = 0.25, p < 0.001).ConclusionsPsA patients seem to have more commonly subclinical airway inflammation than those with only psoriasis. Further studies are needed to replicate these findings.Key Points• Fraction of exhaled nitric oxide (FeNO) is a useful device to detect and monitor airway inflammation not only in asthma but also in systemic inflammatory diseases such as psoriatic arthritis and psoriasis.• Clinicians should be aware to check respiratory diseases in patients with psoriatic arthritis.

Background. Continuous positive airway pressure (CPAP) can be beneficial in acute respiratory failure (ARF) due to coronavirus (COVID-19) pneumonia, but delaying endotracheal intubation (ETI) in nonresponders may increase mortality. We aimed at investigating the performance of composite respiratory indexes as possible predictors of CPAP failure in ARF due to COVID-19. Methods. This was a multicenter, prospective, observational, and cohort study conducted in the respiratory units of three University hospitals in Milan and in a secondary care hospital in Codogno (Italy), on consecutive adult patients with ARF due to COVID-19 pneumonia that underwent CPAP between March 2020 and March 2021. ETI transfer to the intensive care unit or death is defined CPAP failure. Predictors of CPAP failure were assessed before T0 and 1 hour after T1 CPAP initiation and included mROX index (ratio of PaO2/FiO2 to respiratory rate), alveolar-to-arterial (A-a) O2 gradient, and the HACOR (heart rate, acidosis, consciousness, oxygenation, and respiratory rate) score. Results. Three hundred and fifty four patients (mean age 64 years, 73% males) were included in the study; 136 (38.4%) satisfied criteria for CPAP failure. A-a O2 gradient, mROX, and HACOR scores were worse in patients who failed CPAP, both at T0 and T1 (p<0.001 for all parameters). The HACOR score was associated with CPAP failure (odds ratio—OR—for every unit increase in HACOR = 1.361; 95%CI: 1.103–1.680; p=0.004; AUROC = 0.742; p<0.001). CPAP failure was best predicted by a threshold of 4.50 (sensitivity = 53% and specificity = 87%). Conclusions. The HACOR score may be a reliable and early predictor of CPAP failure in patients treated for ARF in COVID-19 pneumonia.

Cigarette smoking is the most important risk factor for Crohn's disease (CD). The effectiveness of smoking cessation programs (SCPs) in patients with CD is still poorly understood. This was a retrospective, observational, single-centre, cohort study of 136 active smokers with mean age 55 years (SD=11), 58% males, including 27 (19.8%) patients with CD who entered the multidisciplinary SCP of the Luigi Sacco University Hospital of Milan from January 2017 through January 2019. A pulmonologist was responsible for the clinical and pharmacological management, while a psychiatrist and a psychologist conducted the counselling and assessed the motivation to quit, anxiety and depression using the Brief Psychiatric Rating Scale (BPRS) and the nicotine dependence with the Fagerström test. Patients were defined as quitters after 12 months. Demographic and clinical characteristics, and Fagerström score, did not differ in patients with and without CD. At baseline, patients with CD had a higher BPRS (median: 27, IQR: 22-32; vs 25 and 22-28.5; p=0.03), and a lower motivation to quit score (median: 10, IQR: 9-13; vs 14 and 12-15; p<0.001). After 12 months, the quitting rate of smokers with CD was significantly lower (14.8% vs 36.7%; p<0.022) and the chance of quitting was negatively associated with the baseline BPRS (r=-0.256; p<0.003). Varenicline and nicotine replacement therapy tended to be less effective in patients with CD. The lower efficacy of SCPs in patients with CD might be secondary to a higher prevalence of anxiety and depression. Psychological issue recognition and support should be enhanced to increase SCP effectiveness in CD.

In the upcoming years, the proportion of elderly patients with chronic obstructive pulmonary disease (COPD) will increase, according to the progressively aging population and the increased efficacy of the pharmacological treatments, especially considering the management of chronic comorbidities. The issue to prescribe an appropriate inhalation therapy to COPD patients with significant handling or coordination difficulties represents a common clinical experience; in the latter case, the choice of an inadequate inhalation device may jeopardize the adherence to the treatment and eventually lead to its ineffectiveness. Treatment options that do not require particular timing for coordination between activation and/or inhalation or require high flow thresholds to be activated should represent the best treatment option for these patients. Nebulized bronchodilators, usually used only in acute conditions such as COPD exacerbations, could fulfill this gap, enabling an adequate drug administration during tidal breathing and without the need for patients' cooperation. However, so far, only short-acting muscarinic antagonists have been available for nebulization. Recently, a nebulized formulation of the inhaled long-acting muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary vibrating mesh nebulizer closed system (SUN-101/eFlow ), has progressed to Phase III trials and is currently in late-stage development as an option for maintenance treatment in COPD. The present critical review describes the current knowledge about the novel nebulizer technology, the efficacy, safety, and critical role of nebulized glycopyrrolate in patients with COPD. To this end, PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for relevant papers. According to the available results, the efficacy and tolerability profile of nebulized glycopyrrolate may represent a valuable and dynamic treatment option for the chronic pharmacological management of patients with COPD.

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets’ air-dispersion and the healthcare workers’ contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment.

Childhood exposure to environmental tobacco smoke (ETS) adversely affects dynamic spirometric indexes as a result of combined early life (including in utero) and current exposure to parental smoking. The aim of our study was to investigate the effect of ETS on lung function and to identify the most sensitive functional parameter for evaluating lung damage. Cross-sectional survey. Health survey on secondary school children. Eighty adolescents boys (mean age ± SD, 16 ± 1 years) classified in three groups: 21 smokers, 30 nonsmokers, and 29 passive smokers. Standardized questionnaire on the smoking habits of the subjects and their parents; assay of urinary cotinine level and measurement of the cotinine/creatine ratio (CCR); and lung function tests, including measurements of lung volumes, spirometric dynamic parameters, and the single-breath diffusing capacity of the lung for carbon monoxide (Dlco). Passive smokers presented a higher residual volume than nonsmokers, and a lower maximal expiratory flow at 25% of FVC (MEF25) and Dlco. Passive smokers whose mothers had smoked during pregnancy had significantly lower MEF25 percentage, Dlco, carbon monoxide transfer coefficient, and diffusion capacity of the alveolar-capillary membrane (Dm) values than did passive smokers whose mothers had given up smoking during pregnancy. Nevertheless, the MEF25 and Dm values of subjects with mothers who had given up smoking during pregnancy were lower than those observed in nonsmokers (p < 0.05), suggesting a negative effect of passive smoking independent of the mother's smoking habit during pregnancy. A statistically significant, negative correlation was found between CCR and Dlco in smokers (r = − 0.63, p < 0.01) and in passive smokers (r = − 0.91, p < 0.001), but not in nonsmokers (r = 0.26, p = not significant), suggesting a dose-effect relationship. Current exposure to ETS in healthy male adolescents is associated with lung function impairment independently of the effects of maternal smoking during pregnancy. More information may be obtained from determining static lung volumes and Dlco.

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April–May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (β −18.675; 95%CI, −28.373–−9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.