Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective.

N-acetyl-L-cysteine (NAC) was initially introduced as a treatment for mucus reduction and widely used for chronic respiratory conditions associated with mucus overproduction. However, the mechanism of action for NAC extends beyond its mucolytic activity and is complex and multifaceted. Contrary to other mucoactive drugs, NAC has been found to exhibit antioxidant, anti-infective, and anti-inflammatory activity in pre-clinical and clinical reports. These properties have sparked interest in its potential for treating chronic lung diseases, including chronic obstructive pulmonary disease (COPD), bronchiectasis (BE), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF), which are associated with oxidative stress, increased levels of glutathione and inflammation. NAC's anti-inflammatory activity is noteworthy, and it is not solely secondary to its antioxidant capabilities. In ex vivo models of COPD exacerbation, the anti-inflammatory effects have been observed even at very low doses, especially with prolonged treatment. The mechanism involves the inhibition of the activation of NF-kB and neurokinin A production, resulting in a reduction in interleukin-6 production, a cytokine abundantly present in the sputum and breath condensate of patients with COPD and correlates with the number of exacerbations. The unique combination of mucolytic, antioxidant, anti-infective, and anti-inflammatory properties positions NAC as a safe, cost-effective, and efficacious therapy for a plethora of respiratory conditions.

Reappraisal of Pidotimod: an immunomodulatory agent with 30-year evidence.

Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) is a synthetic dipeptide with immunomodulatory properties that is indicated for use in adults and children over 3 years of age with documented cell-mediated immunodepression during respiratory and urinary tract infections. Infections are associated with an immune response that helps fight pathogens. In this scenario, inflammatory events occur to improve the antimicrobial reaction. However, defective immunity and/or sustained inflammation may adversely affect the course of the infection. Thus, modulating immune function could be a valuable option in managing patients with infections. The multifaceted mechanism of action of Pidotimod enables it to modulate innate and adaptive immunity. Extensive evidence about Pidotimod, accumulated over the last 30 years, has provided much data on the prevention of recurrent respiratory infections in susceptible children and respiratory exacerbations in patients with chronic bronchitis. Recent studies provide interesting information on how Pidotimod affects the metabolomic profiles of patients with bronchiectasis, clinical and immunological outcomes of elderly patients with pneumonia, clinical and cellular changes in patients with allergic rhinitis and asthma, and beneficial effects on cytokines and humoral immunity in human immunodeficiency virus (HIV) patients. Preliminary experience suggests that Pidotimod can shorten the duration of COVID-19 infection and reduce clinical severity by modulating the immune response, as well as prevent vaccination-related adverse events. In conclusion, the immunomodulatory properties of Pidotimod indicate that it may be a valuable option in managing patients with respiratory infections and other immune-mediated disorders, including allergy, chronic obstructive pulmonary disease, and asthma.

Long-term inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease, cardiovascular disease, and a recent hospitalised exacerbation: The ICSLIFE pragmatic, randomised controlled study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD. METHODS: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death. RESULTS: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events. CONCLUSIONS: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia.

Dysphagia characteristics at FEES examination in post-extubation patients with COVID-19.

Objective: The aims of this study was to analyse fibreoptic endoscopic evaluation of swallowing (FEES) findings in tube-fed patients with coronavirus disease 2019 (COVID-19). Methods: Seventeen patients who had been intubated during intensive care unit (ICU) stay were enrolled. Pooling of secretions, dysphagia phenotype, penetration/aspiration and residue after swallow were assessed through FEES. The Functional Oral Intake Scale (FOIS) scores were also collected. Patients with significant swallowing impairment were evaluated again after 2 weeks. Results: All patients were tube-fed at enrollment. According to the FEES results, 7 started total oral feeding with at least one consistency. The more common dysphagia phenotypes were propulsive deficit and delayed pharyngeal phase. Pooling of secretions, penetration/aspiration, and residue after swallow were frequently documented. A significant improvement in FOIS scores was found during the second FEES examination. Conclusions: Swallowing impairment in patients with severe COVID-19 after discharge from the ICU is characterised by propulsive deficit and delayed pharyngeal phase. Most of these patients required feeding restrictions even if feeding abilities seem to improve over time.

NSAIDs for early management of acute respiratory infections.

PURPOSE OF REVIEW: To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated. RECENT FINDINGS: It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms. SUMMARY: The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

Lung Imaging and Artificial Intelligence in ARDS.

Artificial intelligence (AI) can make intelligent decisions in a manner akin to that of the human mind. AI has the potential to improve clinical workflow, diagnosis, and prognosis, especially in radiology. Acute respiratory distress syndrome (ARDS) is a very diverse illness that is characterized by interstitial opacities, mostly in the dependent areas, decreased lung aeration with alveolar collapse, and inflammatory lung edema resulting in elevated lung weight. As a result, lung imaging is a crucial tool for evaluating the mechanical and morphological traits of ARDS patients. Compared to traditional chest radiography, sensitivity and specificity of lung computed tomography (CT) and ultrasound are higher. The state of the art in the application of AI is summarized in this narrative review which focuses on CT and ultrasound techniques in patients with ARDS. A total of eighteen items were retrieved. The primary goals of using AI for lung imaging were to evaluate the risk of developing ARDS, the measurement of alveolar recruitment, potential alternative diagnoses, and outcome. While the physician must still be present to guarantee a high standard of examination, AI could help the clinical team provide the best care possible.

Early lung diffusion abnormalities and airways' inflammation in children with type 1 diabetes.

BACKGROUND AND AIMS OF THE STUDY: Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls. METHOD: Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test. RESULTS: In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls. CONCLUSIONS: Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.

Respiratory syncytial virus burden and risk factors for severe disease in patients presenting to the emergency department with flu-like symptoms or acute respiratory failure.

BACKGROUND: Predictors of Respiratory Syncytial Virus (RSV) infection and determinants of RSV unfavorable outcomes are still unclear. We assessed RSV burden and investigated the risk factors associated with RSV positive swab and RSV severe disease. METHODS: A retrospective, single center, cohort study included all consecutive patients referred to the emergency department of L. Sacco University Hospital (Milan) with flu-like symptoms or acute respiratory failure (aRF) tested per protocol for SARS-CoV-2, RSV, Influenza A (InvA) during the 2022-2023 autumn/winter season. Clinical characteristics and patients' outcomes were registered. Respiratory failure, need for respiratory support, shock, sepsis or in-hospital death defined severe disease. MAIN FINDINGS: The analysis included 717 patients (65.1% negative swab, 14.1% InvA, 8.5% RSV, 8.6% SARS-CoV-2, 3.6% other viruses). Compared with the study cohort, RSV patients had the highest occurrence of aRF (62.7%) and severe disease (70.5%); mortality was similar to InvA (6.6% vs 5.9%, p = 0.874). Compared with InvA patients, RSV patients were older (p = 0.009), had higher Charlson index (p = 0.001), higher prevalence of chronic heart failure (p = 0.001) and were more frequently on ICS (p = 0.026) and immunosuppressants (p = 0.018). Heart failure [OR (95%CI):3.286 (1.031-10.835); p = 0.041], chronic exposure to ICS [OR (95%CI):2.377 (1.254-4.505); p = 0.008] and immunosuppressants [OR (95%CI):3.661 (1.246-10.754); p = 0.018] predicted RSV infection. Glycaemia ≥120 mg/dL [OR (95%CI):5.839 (1.155-29.519); p = 0.033], leucocytes ≥8000 cells/µL [OR (95%CI):5.929 (1.090-32.268); p = 0.039], and past/active smoking [OR (95%CI):7.347 (1.301-41.500); p = 0.024] predicted severe RSV disease. CONCLUSIONS: RSV infection is associated with significant mortality and morbidity. Preventive strategies for RSV infection such as vaccination are highly warranted, especially in older patients with cardiovascular and chronic respiratory conditions.

Acute dyspnea in the emergency department: a clinical review.

Acute dyspnea represents one of the most frequent symptoms leading to emergency room evaluation. Its significant prognostic value warrants a careful evaluation. The differential diagnosis of dyspnea is complex due to the lack of specificity and the loose association between its intensity and the severity of the underlying pathological condition. The initial assessment of dyspnea calls for prompt diagnostic evaluation and identification of optimal monitoring strategy and provides information useful to allocate the patient to the most appropriate setting of care. In recent years, accumulating evidence indicated that lung ultrasound, along with echocardiography, represents the first rapid and non-invasive line of assessment that accurately differentiates heart, lung or extra-pulmonary involvement in patients with dyspnea. Moreover, non-invasive respiratory support modalities such as high-flow nasal oxygen and continuous positive airway pressure have aroused major clinical interest, in light of their efficacy and practicality to treat patients with dyspnea requiring ventilatory support, without using invasive mechanical ventilation. This clinical review is focused on the pathophysiology of acute dyspnea, on its clinical presentation and evaluation, including ultrasound-based diagnostic workup, and on available non-invasive modalities of respiratory support that may be required in patients with acute dyspnea secondary or associated with respiratory failure.

Criteria to evaluate efficacy of biologics in asthma: a Global Asthma Association survey.

BACKGROUND: Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the evaluation of response to biologics after 4 months of treatment. METHOD: Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts. RESULTS: Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics. CONCLUSIONS: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

The impact of anti-eosinophilic therapy on exercise capacity and inspiratory muscle strength in patients with severe asthma.

Introduction: Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy. Methods: A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis. Results: 14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47-61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake (V'O2 peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy. Conclusion: CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy.

Interventional pulmonology techniques in lung transplantation.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.

Ultrasonographic Assessment of Diaphragmatic Function and Its Clinical Application in the Management of Patients with Acute Respiratory Failure.

Acute respiratory failure (ARF) is a common life-threatening medical condition, with multiple underlying etiologies. In these cases, many factors related to systemic inflammation, prolonged use of steroids, and lung mechanical abnormalities (such as hyperinflation or increased elastic recoil due to pulmonary oedema or fibrosis) may act as synergic mechanisms leading to diaphragm dysfunction. The assessment of diaphragm function with ultrasound has been increasingly investigated in the emergency department and during hospital stay as a valuable tool for providing additional anatomical and functional information in many acute respiratory diseases. The diaphragmatic ultrasound is a noninvasive and repeatable bedside tool, has no contraindications, and allows the physician to rapidly assess the presence of diaphragmatic dysfunction; this evaluation may help in estimating the need for mechanical ventilation (and the risk of weaning failure), as well as the risk of longer hospital stay and higher mortality rate. This study presents an overview of the recent evidence regarding the evaluation of diaphragmatic function with bedside ultrasound and its clinical applications, including a discussion of real-life clinical cases.

High Level of Blood Eosinophils and Localization of Bronchiectasis in Patients with Severe Asthma: A Pilot Study.

Background. Severe asthma and bronchiectasis are heterogeneous diseases that frequently coexist. The location of bronchiectasis is generally determined by specific underlying pathophysiological mechanisms. The aim of this study was to determine whether in a population suffering from both severe asthma and bronchiectasis there was a correlation between eosinophilic inflammation and localization of bronchiectasis. Methods. We enrolled 41 patients with coexisting bronchiectasis from eight different severe asthma center outpatient clinics and collected the following data: baseline characteristics, Asthma Control Test, Asthma Control Questionnaire, IgE level, blood count, high-resolution computed tomography and bronchiectasis-related parameters, skin prick test, FeNO50 and flow-volume spirometry. The study was retrospectively registered. Results. The presence of eosinophils > 1000 cells/µL was related to distribution of lower pulmonary bronchiectasis (9.1% upper lobes vs. 53.3% lower lobes, p = 0.014). Indeed, the presence of eosinophilic counts > 1000 increased the probability of lower localization of bronchiectasis compared to upper lobes (ODD 0.088 (0.010−0.772), p = 0.028). Conclusions. An increase in blood eosinophils > 1000 cells/µL seems to be associated with lower preferential localization of bronchiectasis with sparing of the upper lung lobes. This could represent a new potential radiological phenotype that could have a dedicated therapeutic strategy in the future.

Incidence of Tracheal Stenosis in ICU Hospitalized COVID-19 Patients: Results from a Prospective, Observational, Multicenter Study.

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99-6.8) and 5.4-fold (p = 0.002; CI 1.9-16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Acute Improvements of Oxygenation with Cpap and Clinical Outcomes in Severe COVID-19 Pneumonia: A Multicenter, Retrospective Study.

It is not known if the degrees of improvement in oxygenation obtained by CPAP can predict clinical outcomes in patients with COVID-19 pneumonia. This was a retrospective study conducted on patients with severe COVID-19 pneumonia treated with CPAP in three University hospitals in Milan, Italy, from March 2020 to March 2021. Arterial gas analysis was obtained before and 1 h after starting CPAP. CPAP failure included either death in the respiratory units while on CPAP or the need for intubation. Two hundred and eleven patients (mean age 64 years, 74% males) were included. Baseline median PaO2, PaO2/FiO2 ratio (P/F), and the alveolar-arterial (A-a) O2 gradient were 68 (57−83) mmHg, 129 (91−179) mmHg and 310 (177−559) mmHg, respectively. Forty-two (19.9%) patients died in the respiratory units and 51 (24.2%) were intubated. After starting CPAP, PaO2/FiO2 increased by 57 (12−113; p < 0.001) mmHg, and (A-a) O2 was reduced by 68 (−25−250; p < 0.001) mmHg. A substantial overlap of PaO2, P/F, and A-a gradient at baseline and during CPAP was observed in CPAP failures and successes; CPAP-associated improvements in oxygenation in both groups were similar. In conclusion, CPAP-associated improvements in oxygenation do not predict clinical outcomes in patients with severe COVID-19 pneumonia.