Post-COVID central hypersomnia, a treatable trait in long COVID: 4 case reports.

Introduction: Fatigue is the most commonly reported post-COVID symptom. A minority of patients also report excessive daytime sleepiness, which could be a target for treatment. Methods: Among 530 patients with a post-COVID condition, those with excessive daytime sleepiness were systematically assessed for objective central hypersomnia, with exclusion of all cases not clearly attributable to SARS-CoV-2 infection. Results: Four cases of post-COVID central hypersomnia were identified, three fulfilling the criteria of the 3rd International Classification of Sleep Disorders for idiopathic hypersomnia, and one for type II narcolepsy. We report here their clinical history, sleep examination data and treatment, with a favorable response to methylphenidate in three cases and spontaneous resolution in one case. Conclusion: We highlight the importance of identifying cases of post-COVID central hypersomnia, as it may be a treatable trait of a post-COVID condition.

Dysfunctional breathing symptoms, functional impact and quality of life in patients with long COVID-19: a prospective case series.

BACKGROUND: Dysfunctional breathing is increasingly recognised after SARS-CoV-2 infection, but the associated symptoms, functional impact and quality of life have not been systematically studied. METHODS: This study describes a prospective case series of 48 patients with dysfunctional breathing based on compatible symptoms and an abnormal breathing pattern during cardiopulmonary exercise testing. Patients with underlying disease that could explain these symptoms were excluded. Median time from COVID-19 to evaluation was 212 (IQR 121) days. Self-administered questionnaires, including the Nijmegen questionnaire, Short-Form (36) Health Survey (SF-36), Hospital Anxiety and Depression Scale, modified Medical Research Council scale, post-COVID-19 Functional Scale, and specific long COVID symptoms, were the outcome measures. RESULTS: On average, mean V'O2 was preserved. Pulmonary function tests were within limits of normality. Hyperventilation, periodic deep sighs/erratic breathing and mixed types of dysfunctional breathing were diagnosed in 20.8%, 47.1% and 33.3% of patients, respectively. After dyspnoea, the five most frequent symptoms using the Nijmegen scale with a cut-off of ≥3 were faster/deeper breathing (75.6%), palpitations (63.8%), sighs (48.7%), unable to breathe deeply (46.3%) and yawning (46.2%). Median Nijmegen and Hospital Anxiety and Depression Scale scores were 28 (IQR 20) and 16.5 (IQR 11), respectively. SF-36 scores were lower than the reference value. CONCLUSIONS: Long COVID patients with dysfunctional breathing have a high burden of symptoms, functional impact and a low quality of life, despite no or negligible organic damage.

Dysfunctional breathing diagnosed by cardiopulmonary exercise testing in 'long COVID' patients with persistent dyspnoea.

BACKGROUND: 'Long COVID'-associated dyspnoea may persist for months after SARS-CoV-2 infection. Among the causes of persistent dyspnoea, dysfunctional breathing (DB), defined as an erratic or inappropriate ventilation at rest or exercise, has been observed, but little is known about its occurrence and pathophysiology among individuals with 'long COVID'. We aimed to describe the occurrence and identify clinical predictors of DB among patients following SARS-CoV-2 infection. METHODS: Cardiopulmonary exercise testing (CPET) was performed in 51 SARS-CoV-2 patients (median age, 64 years (IQR, 15)); male, 66.7%) living with 'long COVID' and persistent dyspnoea. CPET was classified into three dominant patterns: respiratory limitation with gas exchange abnormalities (RL); normal CPET or O2 delivery/utilisation impairment (D); and DB. Non-parametric and χ2 tests were applied to analyse the association between CPET dominant patterns and demographics, pulmonary function tests and SARS-CoV-2 severity. RESULTS: Among 51 patients, DB mostly without hyperventilation was found in 29.4% (n=15), RL in 54.9% (n=28) and D in 15.7% (n=8). When compared with RL individuals, patients with DB were younger, had significantly less severe initial infection, a better transfer capacity for carbon monoxide (median 85% (IQR, 28)), higher oxygen consumption (22.9 mL/min/kg (IQR, 5.5)), a better ventilatory efficiency slope (31.6 (IQR, 12.8)), and a higher SpO2 (95% (IQR, 3)). CONCLUSIONS: Our findings suggest that DB without hyperventilation could be an important pathophysiological mechanism of disabling dyspnoea in younger outpatients following SARS-CoV-2 infection, which appears to be a feature of COVID-19 not described in other viral diseases.

[Flexible bronchoscopy: contribution of the anesthesiologis]. / Bronchoscopie souple : apport du médecin anesthésiste.

The field of interventional pulmonology is expanding rapidly with increasingly complex endoscopic procedures. Pulmonologists and anesthesiologists are both airway specialists. When they cooperate in performing flexible bronchoscopies, they must share a common anatomical space. A close and dynamic collaboration helps to optimize patient management by enhancing safety, facilitating the procedures and improving patient satisfaction. Several challenges are to be taken up, notably managing frail and often polymorbid patients, working outside the usual operating-room area, and the need to be quickly available, given the frequently semi-urgent setting of these procedures. In this context, the optimization of collaborative procedures is essential.

Le domaine de la pneumologie interventionnelle est en pleine expansion, avec des procédures endoscopiques de plus en plus complexes. Le pneumologue et le médecin anesthésiste sont deux spécialistes des voies aériennes. Lorsqu'ils coopèrent dans la réalisation des bronchoscopies souples, ils doivent partager un espace anatomique commun. Une collaboration étroite et dynamique permet d'optimiser la prise en charge en renforçant la sécurité, en facilitant la réalisation des procédures et en améliorant la satisfaction du patient. Plusieurs défis sont à relever, notamment la fragilité des patients souvent polymorbides, les conditions de travail hors bloc opératoire et la nécessité de plages d'anesthésie rapidement disponibles au vu d'indications le plus souvent semi-urgentes. Dans ce contexte, l'optimisation des procédures de collaboration est essentielle.

Severe Neuroexcitatory Reaction: A Rare and Underrecognized Life-Threatening Complication of Propofol-Induced Anesthesia.

We describe a case of severe neuroexcitatory reaction with hyperthermia after administration of propofol in a 43-year-old patient suspected of a relapse of sarcoidosis who underwent bronchoscopy. This resulted in a lengthy stay in intensive care and long-term neuropsychological impairment. A review of the literature shows that severe neuroexcitatory symptoms (seizure-like phenomena, abnormal hypertonic, and/or jerky movements) occur rarely after propofol administration and may be life-threatening. Due to the paucity of data, the treatment is mostly empirical. The diagnosis can also be delayed owing to underrecognition. We conclude that health practitioners who frequently use propofol should be aware of this specific manifestation of drug toxicity, which albeit rare can be devastating for the patient.

Long-Term Mechanical Ventilation: Recommendations of the Swiss Society of Pulmonology.

Long-term mechanical ventilation is a well-established treatment for chronic hypercapnic respiratory failure (CHRF). It is aimed at improving CHRF-related symptoms, health-related quality of life, survival, and decreasing hospital admissions. In Switzerland, long-term mechanical ventilation has been increasingly used since the 1980s in hospital and home care settings. Over the years, its application has considerably expanded with accumulating evidence of beneficial effects in a broad range of conditions associated with CHRF. Most frequent indications for long-term mechanical ventilation are chronic obstructive pulmonary disease, obesity hypoventilation syndrome, neuromuscular and chest wall diseases. In the current consensus document, the Special Interest Group of the Swiss Society of Pulmonology reviews the most recent scientific literature on long-term mechanical ventilation and provides recommendations adapted to the particular setting of the Swiss healthcare system with a focus on the practice of non-invasive and invasive home ventilation in adults.

Utility of Rapid On-Site Cytologic Evaluation during Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Malignant and Nonmalignant Disease.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate procedure to sample mediastinal tissue. Rapid on-site cytologic evaluation (ROSE) has been advocated to improve the performance of this procedure, but its benefit remains controversial. Our objective is to assess the utility of ROSE for EBUS-TBNA diagnostic accuracy among unselected patients. METHODS: We prospectively collected data from all consecutive EBUS-TBNA procedures performed between 2008 and 2014. ROSE was introduced since 2011 in our daily practice. The accuracy of EBUS-TBNA with and without ROSE was compared in a univariate and multivariate model accounting for confounding factors. The impact of ROSE was then analyzed according to the etiology and size of the lesions. RESULTS: Among 348 EBUS-TBNA procedures analyzed, 213 were performed with ROSE. The overall accuracy tended to be better with ROSE than without (90.6 vs. 84.4%; p = 0.082). After adjustment in a multivariate model, the benefit of ROSE still did not reach statistical significance (adjusted odds ratio 1.86; 95% confidence interval 0.79-4.41). Similar results were obtained in subgroups of patients with malignant disease or sarcoidosis. The size of the lesion did not influence the impact of ROSE on accuracy. CONCLUSIONS: ROSE was associated with a moderate increase in the accuracy of EBUS-TBNA, but the difference was not statistically significant. The same effect of ROSE was observed in malignant and nonmalignant lesions and this effect was not influenced by the lesion's size.

Development and validation of a simple tool for the assessment of home noninvasive ventilation: the S3-NIV questionnaire.

Patient-centred outcomes are significantly modified by long-term home noninvasive ventilation (NIV), but a short, self-administered, specific tool for routine clinical assessment is lacking. The aim of this study was to develop and validate the S3-NIV questionnaire, a short questionnaire to measure respiratory symptoms, sleep quality and NIV-related side effects.Patients with stable disease who were under long-term home NIV were recruited from three outpatient NIV services. Questionnaire development consisted of a selection of core items for analysis, followed by item reduction, validation and test-retest reliability.338 patients completed a 22-item questionnaire. 11 items were removed because of non-scalability (n=2), redundancy (n=8) and lack of fit (n=1). The final version of the S3-NIV questionnaire consisted of 11 items covering two dimensions: "respiratory symptoms" (Cronbach's α=0.84) and "sleep & NIV-related side effects" (Cronbach's α=0.77). Convergent validity was high between the "respiratory symptoms" subscale of the S3-NIV questionnaire and the St George's Respiratory Questionnaire (rho= -0.76, p<0.001), and between the "sleep & NIV-related side effects" subscale and the Quebec Sleep Questionnaire (rho=0.51, p<0.001). The S3-NIV questionnaire had good test--retest reliability after 4 weeks (intraclass correlation coefficient=0.72).The S3-NIV questionnaire is a short, valid and repeatable self-completed tool for the routine clinical assessment of patients undergoing home NIV.

[Bronchodilatation during spirometry : indications, realization and interpretation]. / Bronchodilatation lors de spirométrie : indications, réalisation et interprétation.

Spirometry with response to short-acting bronchodilators is a key element in the diagnostic work-up of patients with obstructive airways diseases and should be systematically assessed. Response to bronchodilators (RBD) is useful to differentiate asthma from COPD and to grade the severity of obstruction in COPD cases. RBD should not be used to decide for a bronchodilator therapy. An increase in Forced Expiratory Volume in 1 sec (FEV1) or Forced Vital Capacity (FVC) by > 200 ml and 12 % of baseline value is considered as criteria for significant bronchodilator response. With the exception of asthma diagnostic work-up, inhaled therapy should not be interrupted before spirometry. Paradoxical loss of lung function after administration of beta 2 agonists is rarely observed. When present, choice of an alternative bronchodilator agent should be considered.

La spirométrie avec mesure de la réponse aux bronchodilatateurs d'action rapide est un élément diagnostique clé dans le bilan des syndromes obstructifs et doit être systématiquement effectuée. Elle est utile pour distinguer l'asthme de la BPCO et permet de grader la sévérité de l'obstruction en cas de BPCO. On ne devrait pas l'utiliser pour décider du choix d'un bronchodilatateur. On retient comme critère de réversibilité une augmentation du volume expiré maximal en 1 seconde (VEMS) ou de la capacité vitale forcée (CVF) supérieure à 200 ml et 12 % de la valeur de base.Excepté pour le bilan initial d'un asthme, les traitements inhalés ne doivent pas être interrompus avant un bilan spirométrique. Une aggravation paradoxale après bêta-agonistes est une observation rare qui doit faire envisager une alternative à cette classe de bronchodilatateurs.

Unusual presentations and pitfalls of secondary syphilis: osteitis, pneumonia and malignancy.

Syphilis can show unexpected clinical characteristics rendering its diagnosis difficult. We report on two cases of secondary syphilis presenting with atypical histories of knee or cervical pain and cough. Both had bone involvement and one, pulmonary involvement, documented by MRI, CT scan and PCR. Both responded well to therapy with intravenous aqueous penicillin G followed by intramuscular benzathine penicillin G, but a pulmonary adenocarcinoma was diagnosed during follow-up in one case.

Chronic disease management programmes for adults with asthma.

BACKGROUND: The burden of asthma on patients and healthcare systems is substantial. Interventions have been developed to overcome difficulties in asthma management. These include chronic disease management programmes, which are more than simple patient education, encompassing a set of coherent interventions that centre on the patients' needs, encouraging the co-ordination and integration of health services provided by a variety of healthcare professionals, and emphasising patient self-management as well as patient education. OBJECTIVES: To evaluate the effectiveness of chronic disease management programmes for adults with asthma. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, MEDLINE (MEDLINE In-Process and Other Non-Indexed Citations), EMBASE, CINAHL, and PsycINFO were searched up to June 2014. We also handsearched selected journals from 2000 to 2012 and scanned reference lists of relevant reviews. SELECTION CRITERIA: We included individual or cluster-randomised controlled trials, non-randomised controlled trials, and controlled before-after studies comparing chronic disease management programmes with usual care in adults over 16 years of age with a diagnosis of asthma. The chronic disease management programmes had to satisfy at least the following five criteria: an organisational component targeting patients; an organisational component targeting healthcare professionals or the healthcare system, or both; patient education or self-management support, or both; active involvement of two or more healthcare professionals in patient care; a minimum duration of three months. DATA COLLECTION AND ANALYSIS: After an initial screen of the titles, two review authors working independently assessed the studies for eligibility and study quality; they also extracted the data. We contacted authors to obtain missing information and additional data, where necessary. We pooled results using the random-effects model and reported the pooled mean or standardised mean differences (SMDs). MAIN RESULTS: A total of 20 studies including 81,746 patients (median 129.5) were included in this review, with a follow-up ranging from 3 to more than 12 months. Patients' mean age was 42.5 years, 60% were female, and their asthma was mostly rated as moderate to severe. Overall the studies were of moderate to low methodological quality, because of limitations in their design and the wide confidence intervals for certain results.Compared with usual care, chronic disease management programmes resulted in improvements in asthma-specific quality of life (SMD 0.22, 95% confidence interval (CI) 0.08 to 0.37), asthma severity scores (SMD 0.18, 95% CI 0.05 to 0.30), and lung function tests (SMD 0.19, 95% CI 0.09 to 0.30). The data for improvement in self-efficacy scores were inconclusive (SMD 0.51, 95% CI -0.08 to 1.11). Results on hospitalisations and emergency department or unscheduled visits could not be combined in a meta-analysis because the data were too heterogeneous; results from the individual studies were inconclusive overall. Only a few studies reported results on asthma exacerbations, days off work or school, use of an action plan, and patient satisfaction. Meta-analyses could not be performed for these outcomes. AUTHORS' CONCLUSIONS: There is moderate to low quality evidence that chronic disease management programmes for adults with asthma can improve asthma-specific quality of life, asthma severity, and lung function tests. Overall, these results provide encouraging evidence of the potential effectiveness of these programmes in adults with asthma when compared with usual care. However, the optimal composition of asthma chronic disease management programmes and their added value, compared with education or self-management alone that is usually offered to patients with asthma, need further investigation.

Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an emerging endoscopic technique for the diagnosis of peripheral lung lesions. A thorough analysis of ENB's yield and safety is required for comparison to other sampling modalities. OBJECTIVES: To describe ENB's yield and safety profile. METHODS: The MEDLINE and EMBASE databases were systematically searched for studies reporting ENB's yield for peripheral lung lesions. Two independent investigators extracted data and rated each study on a scale of methodological quality. Clearly defined performance outcomes were reconstructed and meta-analyzed. Subgroup analysis and meta-regression were used to identify possible sources of study heterogeneity. RESULTS: A total of 15 trials were included (1,033 lung nodules). A positive and definitive diagnosis was obtained after 64.9% of all ENB procedures (95% CI 59.2-70.3). Overall diagnostic accuracy was 73.9% (95% CI 68.0-79.2). Sensitivity to detect cancer was 71.1% (95% CI 64.6-76.8), with a negative predictive value of 52.1% (95% CI 43.5-60.6). Pneumothorax occurred in 3.1% of patients, requiring chest tube drainage in 1.6% of these cases. Original trials identified 6 variables associated with higher ENB yields: nodule location in the upper or middle lobes, nodule size, lower registration error, presence of a bronchus sign on CT imaging, combined use of an ultrasonic radial probe, and catheter suctioning as a sampling technique. Heterogeneity exploration revealed that studies using general anesthesia or rapid on-site cytological evaluation reported better yields. CONCLUSIONS: ENB is effective and particularly safe. Prospective studies are needed to clarify the role of several variables conditioning the yield of this technique.

[Electromagnetic navigation bronchoscopy for the assessment of peripheral lung nodules]. / Rencontre du "GPS" et du poumon: navigation electromagnétique pour le diagnostic des lésions pulmonaires.

Among recent technological progress, electromagnetic navigational bronchoscopy (ENB), based on the principle of "GPS", allows the bronchoscopist to reach parenchymal lesions situated beyond the field of regular bronchoscopy. Compared to CT-scan guided transthoracic needle aspiration, the yield is lower (65%). However, the rate of complication (pneumothorax, hemorrhage) is significantly lower and the patient is not irradiated. Moreover, the yield remains stable also for cases associated to a lower yield of the transthoracic approach (small and/or deep and/or benign lesion). Beyond the diagnosis of peripheral lung nodules, ENB (alone or in combination with endobronchial ultrasound) is also an efficient and safe tool for disease staging by simultaneous (during the same procedure) sampling of associated hypermetabolic lymph nodes.

[Imported cases of histoplasmosis]. / Cas importés d'histoptasmose.

Histoplasmosis is a fungal infection that may be opportunistic in the context of HIV. Rare in Europe, it is always imported. The two variants of histoplasmosis are encountered in defined geographic areas: var. capsulatum in Americas, Africa and Asia; and var duboisii in Africa only. In immuno-competent patients, acute infection is often asymptomatic, or it may cause a pulmonary syndrome of variable severity. Among immuno-compromised patients, histoplasmosis is disseminated and life-threatening. Diagnosis is typically made by cultures. The treatment of the disseminated form must be started immediately with anti-fungal therapy and highly active anti-retroviral treatment. In a globalized world, one has to remember the importation of unusual exotic diseases.

[Long-term oxygen therapy]. / Oxygénothérapie à domicile.

Two studies showed that continuous long-term oxygen therapy (> 15 h/d) undoubtedly confers a significant benefit on survival in hypoxemic patients with chronic obstructive pulmonary disease. This treatment should be prescribed to stable patients with a PaO2 < 7.3 kPa or a PaO2 < 8 kPa and either previous episodes of ankle edema, pulmonary hypertension or a haematocrit > 55%. Patients who are hypoxemic only during exercise can also benefit from mobile oxygen therapy. However, the Swiss Society of Pneumology does not recommend treating patients with isolated nocturnal hypoxemia, unless they suffer from central apnea and are shown to be responders. The characteristics of the three methods of oxygen delivery for domiciliary treatment are discussed in this review.

Effect of different growth hormone (GH) mutants on the regulation of GH-receptor gene transcription in a human hepatoma cell line.

OBJECTIVE: G to A transition at position 6664 of the growth hormone (GH-1) gene results in the substitution of Arg183 by His (R183H) in the GH protein and causes a new form of autosomal dominant isolated GH deficiency (IGHD type II). The aim of this study was to assess the bioactivity of this R183H mutant GH in comparison with both other GH variants and the 22-kDa GH in terms of GH-receptor gene regulation. DESIGN AND METHODS: The regulation of the GH-receptor gene (GH-receptor/GH binding protein, GHR/GHBP) transcription following the addition of variable concentrations (0, 12.5, 25, 50 and 500 ng/ml) of R183H mutant GH was studied in a human hepatoma cell line (HuH7) cultured in a serum-free hormonally defined medium. In addition, identical experiments were performed using either recombinant human GH (22-kDa GH) as a positive control or two GH-receptor antagonists (R77C mutant GH and pegvisomant (B-2036-PEG)) as negative controls. GHR/GHBP mRNA expression was quantitatively assessed by RT-PCR amplification after 0, 1, 3 and 6 h incubation. RESULTS: Following the addition of R183H mutant GH, GHR/GHBP mRNA changed at a similar rate to that seen in experiments where 22-kDa GH was added, indicating equal bioactivity. At all times and concentrations studied, the addition of R77C mutant GH, however, resulted in a significantly lower increase (P<0.001) of GHR/GHBP mRNA concentration compared with that caused by the addition of either 22-kDa GH or R183H mutant GH. Furthermore, in additional experiments, pegvisomant resulted in an absolute block of GHR/GHBP mRNA expression identical to that seen in control experiments where no 22-kDa GH was added at all. CONCLUSIONS: These data indicate that the R183H mutant GH, although causing an autosomal dominant form of IGHD has an identical effect on GHR/GHBP transcription as its wild-type, the 22-kDa GH. This implies that the IGHD caused by the R183H heterozygous mutation of the GH-1 gene is mainly due to a block of its regulated GH secretion. In addition, the R77C-GH variant and pegvisomant have an antagonistic effect at the level of GHR/GHBP transcription. All these data were confirmed by run-on experiments. In addition, these data highlight, as far as the GH variants are concerned, that a mutational alteration within the GH-1 gene might cause short stature also on the basis of an altered secretory pathway. This fact has to be taken into consideration when growth retardation is clinically diagnosed and studied at the molecular level. Secretory pathways and, therefore, cell-biological mechanisms are of importance and have to be considered in future not only at the scientific but also at the clinical level.