Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. M. Beccaria, M. Luisetti, G. Rodi, A. Corsico, M.C. Zoia, S. Colato, P. Pochetti, A. Braschi, E. Pozzi, I. Cerveri. #ERS Journals Ltd 2004. ABSTRACT: Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits.In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques.More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post-WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75¡19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6¡1.5 kPa (27¡11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels.In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.

Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe symptoms and negative prognosis. Remarkably, the severity of COVID-19 appears to rise with increasing body mass index (BMI). The association between COVID-19 outcomes and overweight/obesity has biological and physiological plausibility. Potential pathophysiological mechanisms that may explain this strong association include the chronic pro-inflammatory state, the excessive oxidative stress response, and the impaired immunity that is commonly reported in these individuals. The role of cytokines, mammalian target of rapamycin (mTOR), and altered natural killer cell polarization in the dangerous liaison between COVID-19 and obesity are discussed here. These pathways can favor and accelerate the deleterious downstream cellular effects of SARS-CoV-2. Moreover, obesity is well known to be associated with reduced lung function and poor response to mechanical ventilation, thus placing these individuals at high risk of severe illness and mortality from COVID-19. Furthermore, obesity may lead to other complications, such as renal failure, cardiovascular dysfunction, hypertension, and vascular damage, which in turn can further accelerate negative clinical outcomes from COVID-19. Obese individuals should be shielded against any potential viral exposure to SARS-CoV-2 with consequential considerations for compulsory protection devices and social distancing. Health care providers should be aware that obesity predisposes to severe symptoms and negative prognosis in COVID-19 patients.

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field.

Obstructive sleep apnea (OSA) and insomnia are the two most common sleep disorders among the general population, and they may often coexist in patients with sleep-disordered breathing (SDB). The higher prevalence of insomnia symptoms in patients with OSA (40–60%) compared to that observed in the general population has thus led researchers to identify a new disorder named comorbid insomnia and OSA (COMISA), whose true burden has been so far largely underestimated. The combined treatment of COMISA patients with positive-airway pressure ventilation (PAP) with cognitive behavioral therapy for insomnia (CBTi) has shown a better patient outcome compared to that obtained with a single treatment. Furthermore, recent evidence has shown that an innovative patient-centered approach taking into consideration patient characteristics, treatment preferences and accessibility to treatment is recommended to optimize clinical management of COMISA patients. However, in this complex mosaic, many other sleep disorders may overlap with COMISA, so there is an urgent need for further research to fully understand the impact of these therapies on outcomes for OSA patients with comorbidity. In light of this need, this review focuses on the major sleep disorders comorbid with OSA and the recent advances in the management of these insomniac patients.

Sleep health and its adaptation to individual and environmental factors are crucial to promote physical and mental well-being across animal species. In recent years, increasing evidence has been reported regarding the relationship between sleep and the immune system and how sleep disturbances may perturb the delicate balance with severe repercussions on health outcomes. For instance, experimental sleep deprivation studies in vivo have reported several major detrimental effects on immune health, including induced failure of host defense in rats and increased risk for metabolic syndrome (MetS) and immune suppression in humans. In addition, two novel risk factors for dysregulated metabolic physiology have recently been identified: sleep disruption and circadian misalignment. In light of these recent findings about the interplay between sleep and the immune system, in this review, we focus on the relationship between sleep deprivation and immunity against viruses, with a special interest in SARS-CoV-2 infection.

Previous studies showed a bidirectional relationship between renal function decline and obstructive sleep apnea (OSA) syndrome. Continuous Positive Airway Pressure (C-PAP) treatment was shown to preserve the kidney function in OSA patients. This study aims to investigate the progression of long-term renal function in OSA patients treated with different PAP strategies (patients were divided into two groups, fixed C-PAP or other PAP—automatic and bilevel pressure). Comorbidities and 10-years survival were also evaluated. We performed a retrospective, observational, single-center, cohort study, including the first 40 consecutive patients enrolled from 2009 in the Respiratory disease Unit at the Vercelli University Hospital database. The patient inclusion criteria were: age ≥ 18 years with OSA syndrome according to AASM (American Academy of Sleep Medicine) guidelines. Creatinine serum levels (mg/dL) and the estimated Glomerular Filtration Rate (eGFR, mL/min calculated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration equation)) were measured at 3 different time points: at baseline, 3 years and 8 years after PAP treatment. The Kaplan–Meier survival curves stratified according to PAP treatment and compliance have been reported together with log-rank test estimation. In our study, we found a significant creatinine serum level reduction after 3 years of fixed C-PAP treatment (p value = 0.006) when compared to baseline values. However, we observed that the long-term C-PAP benefit was not significant (p value = 0.060). Our data confirmed the progressive renal function decline in OSA patients, especially in those using other-PAP treatments; nevertheless, OSA treatment with a fixed C-PAP device has shown, in the short term, a significant improvement in renal function. By contrast, in our study, long-term benefits after 8 years are not been demonstrated probably because of the lack of compliance of the patients and the aging effect.

Sleep-related breathing disorders (SBDs) are characterized by abnormal respiration during sleep. Obstructive sleep apnea (OSA), a common SBD increasingly recognized by physicians, is characterized by recurrent episodes of partial or complete closure of the upper airway resulting in disturbed breathing during sleep. OSA syndrome (OSAS) is associated with decreased patients' quality of life (QoL) and the presence of significant comorbidities, such as daytime sleepiness. Similarly to what seen for OSAS, the prevalence of asthma has been steadily rising in recent years. Interestingly, severe asthma (SA) patients are also affected by poor sleep quality—often attributed to nocturnal worsening of their asthma—and increased daytime sleepiness and snoring compared to the general population. The fact that such symptoms are also found in OSAS, and that these two conditions share common risk factors, such as obesity, rhinitis, and gastroesophageal reflux, has led many to postulate an association between these two conditions. Specifically, it has been proposed a bidirectional correlation between SA and OSAS, with a mutual negative effect in term of disease severity. According to this model, OSAS not only acts as an independent risk factor of asthma exacerbations, but its co-existence can also worsen asthma symptoms, and the same is true for asthma with respect to OSAS. In this comprehensive review, we summarize past and present studies on the interrelationship between OSAS and SA, from endo-phenotype to clinical aspects, highlighting possible implications for clinical practice and future research directions.

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