The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) .

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups—between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060–0.141) and 0.099 L (95% BCI, 0.048–0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Severe cases of COVID‐19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID‐19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo‐capillary barriers. The authors performed a systematic literature review and random‐effects meta‐analysis to determine the potential value of MSC therapy for treating COVID‐19‐infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2/FiO2 ratio, alveolo‐capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.

The emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) at the end of 2019 in Hubei province China, is now the cause of a global pandemic present in over 150 countries. COVID-19 is a respiratory illness with most subjects presenting with fever, cough and shortness of breath. In a subset of patients, COVID-19 progresses to hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), both of which are mediated by widespread inflammation and a dysregulated immune response. Mesenchymal stem cells (MSCs), multipotent stromal cells that mediate immunomodulation and regeneration, could be of potential benefit to a subset of COVID-19 subjects with acute respiratory failure. In this review, we discuss key features of the current COVID-19 outbreak, and the rationale for MSC-based therapy in this setting, as well as the limitations associated with this therapeutic approach.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancerassociated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer. ª 2019 Steunstichting ESOT

Objectives:Gastroesophageal reflux is common in patients post-lung transplantation (LTx) and thus considered a risk factor for aspiration and consequently allograft rejection and the development of chronic allograft failure. However, evidence supporting this remains unclear and often contradictory. Our aim was to examine the role played by esophageal motility on gastroesophageal reflux exposure, along with its clearance and that of boluses swallowed, and the relationship to development of obstructive chronic lung allograft dysfunction (o-CLAD).Methods:Patients post-LTx (n=50, 26 female; mean age 55 years (range, 20–73 years)) completed high-resolution impedance manometry and 24-h pH/impedance. Esophageal motility abnormalities were classified based upon the Chicago Classification version 3.0.Results:Esophagogastric junction outflow obstruction alone (EGJOOa) (P=0.01), incomplete bolus transit (IBT) (P=0.006) and proximal reflux (P=0.042) increased the risk for o-CLAD. Patients with EGJOOa were most likely to present with o-CLAD (77%); despite being less likely to exhibit abnormal numbers of reflux events (10%) compared with those with normal motility (o-CLAD: 29%, P<0.05; abnormal reflux events: 64%, P<0.05). Patients with EGJOOa had lower total reflux bolus exposure time than those with normal motility (0.6 vs. 1.5% P<0.05). In addition, poor esophageal clearance documented by abnormal post-reflux swallow-induced peristaltic wave index associated with o-CLAD; inversely correlating with the proportion of reflux events reaching the proximal esophagus (r=−0.251; P=0.052).Conclusions:These observations support esophageal dysmotility, especially EGJOOa, and impaired clearance of swallowed bolus or refluxed contents, more so than just the presence of gastroesophageal reflux alone, as important risk factors in the development of o-CLAD.

A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum cases hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus and prednisone for seven days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over six days. Plasma ammonia concentrations were determined and compared using Wilcoxon ranks sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth [median, 188 μmol/L; range, 102–340 μmol/L] were similar to those of normal [median, 226 μmol/L; range, 154–284 μmol/L, p>0.05], uninfected immunosuppressed [median, 231 μmol/L; range, 122–340 μmol/L, p>0.05], and U. parvum IT/IP challenged immunocompetent [median, 226 μmol/L; range, 130–330 μmol/L, p>0.05] mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136–1,000 μmol/L) or IP (median 307 μmol/L; range 132–692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p<0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice.

Background: The coronavirus disease 2019 (COVID-19) has been identified in over 110 million people with no studies comparing pre-infection pulmonary function to post-infection. This study's aim was to compare preinfection and post-infection pulmonary function tests (PFT) in COVID-19 infected patients to better delineate between preexisting abnormalities and effects of the virus. Methods: This was a retrospective multi-center cohort study. Patients were identified based on having COVID-19 and a pre-and post-infection PFT within one year of infection during the time period of March 1, 2020 to November 10, 2020. Findings: There was a total of 80 patients, with an even split in gender; the majority were white (n = 70, 87¢5%) and never smokers (n = 42, 52¢5%). The majority had mild to moderate COVID-19 disease (n = 60, 75¢1%) with 25 (31¢2%) requiring hospitalization. There was no difference between the pre-and post-PFT data, specifically with the forced vital capacity (FVC) (p = 0¢52), forced expiratory volume in 1 s (FEV1) (p = 0¢96), FEV1/FVC(p = 0¢66), total lung capacity (TLC) (p = 0¢21), and diffusion capacity (DLCO)(p = 0¢88). There was no difference in the PFT when analyzed by hospitalization and disease severity. After adjusting for potential confounders, interstitial lung disease (ILD) was independently associated with a decreased FEV1 (-2¢6 [95% CI, -6¢7 to -1¢6] vs. -10¢3 [95% CI, -17¢7 to -2¢9]; p = 0¢03) and an increasing age (p = 0¢01) and cystic fibrosis (-1¢1 [95% CI, -4¢5 to-2¢4] vs. -36¢5 [95% CI, -52¢1 to -21¢0]; p < 0¢01) were associated with decreasing FVC when comparing pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC (p = 0¢01) and DLCO (p = 0¢02) before and after infection. Interpretation: This study showed that there is no difference in pulmonary function as measured by PFT before and after COVID-19 infection in non-critically ill classified patients. There could be a relationship with certain underlying lung diseases (interstitial lung disease and cystic fibrosis) and decreased lung function following infection. This information should aid clinicians in their interpretation of pulmonary function tests obtained following COVID-19 infection.