Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Individual modeling of oxygen capture by the human lungs.

It has been proposed that oxygen capture by the human lungs depends on four determinants: ventilation, cardiac output, oxygen partial pressure in the inspired air and the venous blood. Indeed, the theoretical-numerical model proposed recently by Kang et al. was able to interpret the known empirical relation between the average of the determinants and the average oxygen capture called VO2. This method is tested here at the individual level in a group of 31 subjects submitted to standard pulmonary function testing and cardiopulmonary exercise testing. For this, an inverse method is used in which individual cardiac output is predicted from the clinical test data. Comparison to the cardiac output deduced from Fick principle confirms that the dynamic model is a "microscopic" justification of the "macroscopic" Fick principle. It shows that in addition to the four determinants, two secondary determinants, namely hemoglobin concentration and Bohr effect, expressed here through P50, play significant roles.

[Guidelines for methacholine provocation testing]. / Recommandations pour le test de provocation bronchique à la méthacholine en pratique clinique, à partir de l'âge scolaire.

Bronchial challenge with the direct bronchoconstrictor agent methacholine is commonly used for the diagnosis of asthma. The "Lung Function" thematic group of the French Pulmonology Society (SPLF) elaborated a series of guidelines for the performance and the interpretation of methacholine challenge testing, based on French clinical guideline methodology. Specifically, guidelines are provided with regard to the choice of judgment criteria, the management of deep inspirations, and the role of methacholine bronchial challenge in the care of asthma, exercise-induced asthma, and professional asthma.

[Study about the prevalence of the obstructive sleep apnoea syndrome in Vietnam]. / Étude de la prévalence du syndrome d'apnées obstructives du sommeil au Vietnam.

INTRODUCTION: Epidemiological studies on obstructive sleep apnoea syndrome (OSAS) in Asia, South East Asia in particular, are few. The EPSASIE study aimed to determine the prevalence of OSAS in an adult Vietnamese population and to describe its characteristics. METHODS: This is a prospective, observational, multicenter study. Nocturnal ventilatory polygraphy (PV) or polysomnography (PSG) were performed in patients having symptoms evocative of the SAS syndrome and an index of respiratory events (IER)>10/h or>25 in one hour, measured by RU Sleeping. RESULTS: A total of 667/750 validated questionnaires were received. The mean age of the study population was 44±12 years with a mean body mass index of 21.6±5.2kg/m2. PV or PSG were performed on 93 subjects after positive screening by RU Sleeping. OSAS with an apnoea-hypopnoea index (AHI)>5 was found in 57 subjects (8.5%) and in 35 subjects with AHI>15 (5.2% of cases). CONCLUSION: The prevalence of OSAS is quite high in the Vietnamese population and comparable with current literature data.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

The DLNO/DLCO ratio: Physiological significance and clinical implications.

DLNO/DLCO directly measures the ratio of the diffusing capacities of the lung for nitric oxide (NO) and carbon monoxide (CO). In terms of the Roughton and Forster (1957) equation, 1/DL=1/Dm+1/θVc, where Dm is the membrane (Dm) and θVc is the red cell component of the overall diffusing conductance (DL); DLNO mostly reflects the Dm component and DLCO the θVc red cell component. The DLNO/DLCO ratio is positively related to the DmCO/Vc ratio and the CO red cell resistance (1/θCOVc) as a percentage of the total resistance (1/DLCO), independent of the absolute values of DLNO or DLCO. In clinical studies, a raised DLNO/DLCO ratio (≥110% predicted versus a control group), plus a low DLNO and DLCO (<67% pred), predicts pulmonary vascular disease, while a low DLNO/DLCO ratio, with similarly reduced DLNO and DLCO, is associated with interstitial lung disease with fibrosis. More clinical studies are needed, and reference values need to be better defined.

Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis.

Fibrosis is characterized by disproportionate accumulation of collagens and other extracellular matrix substances, resulting in organ dysfunction and failure. In systemic sclerosis, cellular and molecular mechanisms involved in the pathophysiology of fibrosis are highly complex and yet barely understood. Anatomopathological findings showed the coexistence of patchy inflammatory cell infiltration, microvascular injuries, and fibrotic foci. One of the most commonly accepted hypotheses considers endothelial activation as the triggering phenomenon inducing inflammatory and autoimmunity activation. The resulting cytokines and autoantibodies production accelerates the proliferating rate of normal fibroblasts and their transformation into myofibroblasts, leading to diffuse fibrosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis.

Contribution of exhaled nitric oxide measurement in airway inflammation assessment in asthma. A position paper from the French Speaking Respiratory Society.

Nitric oxide (NO) is both a gas and a ubiquitous inter- and intracellular messenger with numerous physiological functions. As its synthesis is markedly increased during inflammatory processes, NO can be used as a surrogate marker of acute and/or chronic inflammation. It is possible to quantify fractional concentration of NO in exhaled breath (FENO) to detect airway inflammation, and thus improve the diagnosis of asthma by better characterizing asthmatic patients with eosinophilic bronchial inflammation, and eventually improve the management of targeted asthmatic patients. FENO measurement can therefore be viewed as a new, reproducible and easy to perform pulmonary function test. Measuring FENO is the only non-invasive pulmonary function test allowing (1) detecting, (2) quantifying and (3) monitoring changes in inflammatory processes during the course of various respiratory disorders, including corticosensitive asthma.

[Use of pulmonary function tests and biomarkers studies to diagnose and follow-up interstitial lung disease in systemic sclerosis]. / Intérêts des explorations fonctionnelles respiratoires et des études des biomarqueurs dans le diagnostic et le suivi évolutif de la pneumopathie interstitielle diffuse dans la sclérodermie systémique.

Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis.

Exhaled nitric oxide concentration and decompression-induced bubble formation: An index of decompression severity in humans?

INTRODUCTION: Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or following a wet dive. The underlying mechanisms of this decrease remain however unknown. The aim of this study was to quantify the separate effects of submersion, hyperbaric hyperoxia exposure and decompression-induced bubble formation on FE NO after a wet dive. METHODS: Healthy experienced divers (n=31) were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded with the KISS score. Before and after each dive FE NO values were measured using a hand-held electrochemical analyzer. RESULTS: There was no change in post-dive values of FE NO values (expressed in ppb=parts per billion) in the Air dive group (15.1 ± 3.6 ppb vs. 14.3 ± 4.7 ppb, n=9, p=0.32). There was a significant decrease in post-dive values of FE NO in the Oxygen dive group (15.6 ± 6 ppb vs. 11.7 ± 4.7 ppb, n=9, p=0.009). There was an even more pronounced decrease in the deep dive group (16.4 ± 6.6 ppb vs. 9.4 ± 3.5 ppb, n=13, p<0.001) and a significant correlation between KISS bubble score >0 (n=13) and percentage decrease in post-dive FE NO values (r=-0.53, p=0.03). DISCUSSION: Submersion and hyperbaric hyperoxia exposure cannot account entirely for these results suggesting the possibility that, in combination, one effect magnifies the other. A main finding of the present study is a significant relationship between reduction in exhaled NO concentration and dive-induced bubble formation. We postulate that exhaled NO concentration could be a useful index of decompression severity in healthy human divers.

Early inhaled nitric oxide at high dose enhances rat lung development after birth.

RATIONAL: Inhaled nitric oxide (NO) is frequently administered to full term and preterm newborns in various clinical settings in order to alleviate pulmonary hypertension whilst improving oxygenation. However, the physiological effect of NO on early postnatal lung development has not yet been clearly described. We therefore investigated whether NO administered by inhalation affects lung development at early postnatal life. METHODS: Pregnant rats were placed in a chamber containing 5 ppm (iNO-5 ppm group) and 20 ppm NO (iNO-20 ppm group), started from the last day of their pregnancy in order to keep rat pups under ambient NO from birth to 7 days postnatal. Control animals were kept at room air and all rat pups were sacrificed at postnatal day 7 and day 14. RESULTS: Lung-to-body weight and wet-to-dry lung weight ratios did not significantly differ among 3 groups at postnatal day 7 and day 14. Vascular volume densities (Vv) in both NO groups (5 and 20 ppm) were higher than controls (P<0.05; P<0.001). Pulmonary vessel number was significantly increased in iNO-20 ppm group. Radial alveolar counts (RAC) and mean linear intercepts (MLI) markedly increased (consistent with increased alveolarization) in iNO-20 ppm group. This was associated with upregulation of VEGF/VEGFR-2, MT1-MMP/MMP2 and HO-1 protein expression in iNO-20 ppm group. CONCLUSIONS: We concluded that inhaled NO at 20 ppm enhanced lung development possibly through increased expression of HO-1, VEGF/VEGFR-2, and MMP2 at early stage of postnatal rat life.

[Pulmonary hypertension: from molecular pathophysiology to haemodynamic abnormalities]. / Hypertension pulmonaire: de la physiopathologie moléculaire aux anomalies hémodynamiques.

Pulmonary hypertension (PH) is a complex disorder resulting from many etiologies that cause disturbances of normal pulmonary haemodynamics. Recent breakthroughs have led to a better understanding of the pathophysiology of the disease. In PH, haemodynamic disturbances are closely linked to structural changes and excessive remodeling of pulmonary vessels, leading to progressive narrowing of the pulmonary vascular lumen. Imbalances between pulmonary vasoconstrictors and vasodilators on the one hand, and factors favoring cell proliferation and apoptosis on the other hand, probably account for most cases of PH. This review aims to update readers with the current knowledge on the molecular physiopathology of PH and how this can progress the therapeutic of this disorder.

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.