COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Northern Greece during 2020-2022: A Comparative Study According to the Main Consensus Criteria and Definitions.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure due to SARS-CoV-2 infection. Almost 2.5 years since the start of the COVID-19 pandemic, it continues to raise concerns as an extra factor that contributes to increased mortality, which is mostly because its diagnosis and management remain challenging. The present study utilises the cases of forty-three patients hospitalised between August 2020 and February 2022 whose information was gathered from ten ICUs and special care units based in northern Greece. The main aim was to describe the gained experience in diagnosing CAPA, according to the implementation of the main existing diagnostic consensus criteria and definitions, and present the different classification of the clinical cases due to the alternative algorithms.

Persistent Sleep Quality Deterioration among Post-COVID-19 Patients: Results from a 6-Month Follow-Up Study.

Background: To date, evidence about sleep disturbances among post-COVID-19 patients is limited. This study aimed to evaluate sleep quality after hospitalization due to SARS-CoV-2 infection. Methods: In-person follow-up was conducted in patients with prior hospitalization due to COVID-19 1(Τ1), 3(Τ2), and 6 (Τ3) months after hospital discharge. Patients were asked to complete questionnaires concerning sleep quality: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Athens Insomnia Scale (AIS), the Fatigue Severity Scale (FSS), and the Stop-BANG (S-B) questionnaire. Results: In total, 133 patients were enrolled (mean age: 56.0 ± 11.48 years, 59.4% males). The most frequently reported comorbidity was arterial hypertension (29.8% of patients), while 37.4% of patients had no comorbidities. The majority of participants exhibited poor sleep quality (global PSQI ≥ 5) at T1 (84.3%), T2 (75.7%), and T3 (77.4%). Insomnia was observed in 56.5%, 53.5%, and 39.2% of participants, respectively (AIS ≥ 6). An FSS score ≥ 4 was observed in 51.2%, 33.7%, and 29.1% of participants at T1, T2, T3, respectively. Elapsed time was found to be negatively and independently associated with the global PSQI, PSQI C5-Sleep disturbance, PSQI C7-Daytime dysfunctions, FSS, and AIS after adjustment for possible confounders. No significant difference was found between groups with good and poor sleep quality (based on the global PSQI) with respect to gender (p = 0.110), age (p = 0.528), BMI (p = 0.816), smoking status (p = 0.489), hypertension (p = 0.427), severity of disease (p = 0.224), the Charlson Comorbidity Index (p = 0.827), or the length of hospital stay (p = 0.162). Participants with excessive daytime sleepiness (EDS) and patients with severe fatigue (FSS ≥ 4) were significantly younger. Females presented a higher rate of insomnia symptoms (55.7% vs. 44.3%, p < 0.001). Conclusions: Several sleep disturbances were observed after hospital discharge for COVID-19 pneumonia at certain time points; However, the improvement over time was remarkable in most domains of the assessed questionnaires.

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics.

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.

Impaired Cardiovascular Response to Exercise in Patients with Severe Asthma: A Case-Control Study.

Background: Although asthmatics may present reduced exercise capacity, data on their cardiovascular responses during exercise testing have been scarcely investigated. The aim of this pilot case-control study is to test: a) whether double product (DP), an index of cardiovascular reserve, differs among patients with severe and mild-moderate asthma, and b) whether DP is associated with asthma control level, physical activity (PA) and exercise capacity, in asthmatics population. Materials and Methods: A group of patients with severe asthma (group S) and a matched group of patients with mild-moderate asthma (group M) was studied. All participants completed asthma control and physical activity (IPAC) questionnaires, lung function measurements and six-minute walk test. The exercise capacity (as 6-minute walk distance (6MWD) and corresponding work), the Borg Dyspnea, the rating of perceived excursion and the average PA METS were recorded. Results: A total of 18 patients were studied. DP at exercise end was significantly lower in group S, compared to group M (16412.2±4732.1 vs. 18594.8±3984.4 mmHgXbpm; p=0.041) and was moderately associated with % predicted 6MWD (r=0.592; p=0.001). Group S patients were also presented with lower moderate intensity PA, compared to group M, while exercise capacity was similar between the groups. Asthma control level had no impact on exercise capacity nor PA parameters. Conclusion: Patients with severe asthma may have impaired cardiovascular reserve as established by DP, even when exercise capacity is indifferent from patients with milder disease. As an easy-to-assess parameter, DP may offer further information in the functional evaluation of these patients.

Diffuse Alveolar Hemorrhage after Receiving Oral Levonorgerstrel for Emergency Contraception: A Case Report.

INTRODUCTION: Drug-induced diffuse alveolar hemorrhage (DAH) has been associated with the administration of various medications, among which levonorgestrel (LN) has not been reported until now. CASE PRESENTATION: This case study describes a 42-year-old woman who presented with hemoptysis, hypoxemia, and radiological depiction of ground glass opacities, 3 days after she had received emergency contraceptive medication containing levonorgestrel. Emergent bronchoscopy was performed, and BAL was diagnostic of diffuse alveolar hemorrhage (DAH). A thorough diagnostic approach was followed, in order to detect the underlying pathological condition that induced DAH. The absence of other identifiable pathological conditions in this patient raised suspicion of LN's potential causative role. CONCLUSION: DAH has not been reported as an adverse effect of LN until now. However, LN has been found to exert immunomodulatory effects and to present potential for manifestations of vasculitis as well as severe hypersensitivity reactions. These mechanisms may have been implicated in the development of DAH in our patient, who presented no other pathological conditions.

Clinical and pathophysiological characteristics of valproate-induced pleural effusion.

INTRODUCTION: Valproic acid is a carboxylic acid derivative commonly prescribed for several types of seizure disorders or for acute manic episodes in patients with bipolar disorder. Several cases of valproate-induced pleural effusion have been reported, although the precise pathophysiological mechanism remains unknown. OBJECTIVE: To describe the presentation of pleural effusion associated with valproate use and to categorize published case reports according to clinical, immunological, and pleural effusion cell type. METHODS: PubMed/MEDLINE and Embase databases were systematically searched from January 1970 until November 2020 using the following search terms: "valproic acid" OR "valproate" OR "pleural fluid" OR "exudative effusion" OR "transudative effusion" OR "valproic lung adverse events". These searches yielded 171 references of which 135 articles were considered irrelevant, leaving 36 potentially relevant references which were carefully scrutinized. Twenty-eight cases of valproate-induced pleural effusion were identified after excluding two articles reporting five patients with lung parenchymal adverse reactions to treatment with valproic acid; two articles reporting three patients in whom the pleural effusion could not be attributed to valproic acid alone; one case discussing valproate therapy and fungal pleural effusion; and one describing a patient who suffered from severe cardiac failure. There were also two cases, in an abstract form, with pericardial and pleural effusion, but without any further informative details, and, thus, they were also excluded from this survey. EXUDATIVE EOSINOPHILIC PLEURAL EFFUSION: This was the most common type of valproate-induced pleural effusion reported in 17 out of 28 cases (60.7%), with concurrent peripheral eosinophilia in ten. Acute hypersensitivity reaction, inflammation of the pleural cavity induced by the drug, drug toxicity, and damage to mesothelial cells due to oxidants, comprise the possible pivotal mechanisms. EXUDATIVE LYMPHOCYTIC PLEURAL EFFUSION: This was reported in two cases, with concurrent pericardial effusion in one. Discontinuation of valproate led to resolution of the effusion, although the underlying pathophysiological mechanisms remain abstruse. Interestingly, a patient presented with recurrent pleural effusion characterized by transition from eosinophilic to lymphocytic predominance after readministration of valproate. TRANSUDATIVE PLEURAL EFFUSION: Three out of 28 cases (10.7%) were characterized by neutrophilic transudative pleural effusion after long-term therapy with valproate, while concurrent pericardial effusion was also noted in two. VALPROATE-INDUCED LUPUS ERYTHEMATOSUS WITH PLEURAL EFFUSION: Five patients receiving valproate therapy (17.9% out of the 28 cases) developed drug-induced lupus erythematosus with concurrent pleural effusion that was eosinophilic in three. All patients had positive antinuclear antibodies; anti-histone antibodies were positive in two. CONCLUSIONS: Valproate-induced pleural effusion is rare, but patients receiving treatment with valproic acid who develop respiratory symptoms should be examined for valproate-induced pleural effusion.

Changes in the respiratory function of COVID-19 survivors during follow-up: A novel respiratory disorder on the rise?

BACKGROUND: The Human Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory disorder that may result in acute respiratory distress syndrome. The aim of this review was to investigate the incidence and type of respiratory function abnormalities during the follow-up of patients who recovered from COVID-19. METHODS: A systematic search of MEDLINE was conducted, utilising various term combinations. Studies that assessed any respiratory function parameter during the re-evaluation of patients who recovered from COVID-19 and were published as full-text articles in English are included in this review. RESULTS: Amongst 183 articles initially retrieved, 8 fulfilled the criteria and were included in this review; they involved a total of 341 adult patients. Four were retrospective studies, one was a prospective cohort study, one was a randomised control trial and two were case reports/case series. The follow-up time ranged from 1 month since symptom onset to 3 months after discharge. The most frequent abnormality was reduced lung diffusion for carbon monoxide (DLCO), followed by a restrictive pattern. Other findings are the lack of resting hypoxemia, the reduced respiratory muscle strength and the decreased exercise capacity, although relative data are extremely limited. CONCLUSION: Patients who recovered from COVID-19 present with abnormal respiratory function at short-term follow-up, mainly with reduced lung diffusion and a restrictive pattern. However, results are currently very limited in order safe conclusions to be made, regarding the exact incidence of these abnormalities and whether they may be temporary or permanent.

The presence of insomnia and depression contributes to the acceptance of an initial treatment trial of continuous positive airway pressure therapy in patients with obstructive sleep apnea.

The presence of comorbid insomnia and sleep apnea (COMISA) reduces the initial acceptance of continuous positive airway pressure (CPAP) therapy in 39-58% of patients with obstructive sleep apnea (OSA). Depressive disorders are reported in 5 to 63% of patients with OSA. Here we studied the co-occurrence of depression and insomnia in OSA patients and its impact on treatment acceptance in a real-life controlled trial. METHODS: In this prospective, uncontrolled study, participants were recruited from January to December 2018, among adult patients who visited our sleep lab. Participants underwent polysomnography study and completed the Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Zung Depression Rating Scale (ZDRS). All subjects were categorized into 8 groups: no OSA/no depression (apnea-hypopnea index [AHI] < 5/h, n = 34), mild OSA/no depression (AHI = 5-14/h, n = 22), moderate OSA/no depression (AHI = 15-29/h, n = 44), severe OSA/no depression (AHI ≥ 30/h, n = 45), no OSA/mild depression (AHI < 5/h, n = 31), mild OSA/mild depression (AHI = 5-14/h, n = 24), moderate OSA/mild depression (AHI = 15-29/h, n = 31), and severe OSA/mild depression (AHI ≥ 30/h, n = 40). RESULTS: Over the one-year period, 272 participants (200 men, mean age 52.9 ± 13.0 years, BMI 33.6 ± 7.2 kg/m2) were enrolled. When the above 8 groups were subcategorized into the presence or absence of insomnia, we found no differences in CPAP trial acceptance between subgroups except in patients from the mild depression/severe OSA/insomnia subgroup who denied CPAP therapy more frequently (chi-squared test p = 0.016). We found, with a moderate efficiency indicated by the ROC curve, that patients with AHI > 15/h, AIS ≥ 11, and ZDRS > 44 were more likely to refuse an initial trial of CPAP treatment because of COMISA and depression (ROC curve area = 0.710, p = 0.049). CONCLUSION: This study demonstrates that it is important to recognize a depressive mood disorder in patients with moderate/severe OSA and COMISA as the coexistence of these comorbidities impairs the rate of initial acceptance of CPAP treatment. Additionally, our study suggests the cut-off values from the AIS and ZDRS questionnaires to help lead clinicians to an early diagnostic evaluation of COMISA patients for the presence of depressive mood disorder.