Two women with unexplained dyspnoea: removing the blame game from the lungs.

Hypoxaemia due to right-to-left atrial shunt with normal pressures in the right heart cavities represents an underdiagnosed condition. A systematic approach to hypoxaemic respiratory failure based on pathophysiology can lead to an accurate diagnosis. https://bit.ly/4bTP8fJ.

Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease.

Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.

The impact of cardiovascular comorbidities associated with risk for left heart disease on idiopathic pulmonary arterial hypertension: Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or <3 CVCs, arterial hypertension, diabetes mellitus, obesity, presence of coronary artery disease, or atrial fibrillation. Overall, 77 patients with IPAH (55.1 [interquartile range, IQR: 24.1] years, 62.8% women) have been recorded. Fifteen patients (19.2%) had ≥3 CVCs, while 25 (32%) were over 65 years old. Patients with ≥3 CVCs were older, presented an almost equal female to male ratio, walked less in 6-min walk test, and had lower mean arterial pulmonary pressure and pulmonary vascular resistance at baseline than patients with less CVCs. Fewer patients with ≥3 CVCs received PAH-specific treatment compared to patients with less comorbidities (n = 11 [73.3%] versus n = 58 [95.5%], p = 0.02). During a median follow-up period of 3.8 (IQR: 2.7) years, 18 patients died (all-cause mortality 24.3%). Male sex and older age were independent predictors of mortality and/or lung transplantation, while CVCs did not have a significant impact on clinical outcomes. In this nationwide, register-based study, the epidemiology of IPAH involves older patients with CVCs, who seem to have less hemodynamic compromise, but worse functional impairment and are treated less aggressively with PAH pharmacotherapy.

Respiratory system as the main determinant of dyspnea in patients with pulmonary hypertension.

Dyspnea on exertion is a devastating symptom, commonly observed in patients with pulmonary hypertension (PH). The pathophysiology of dyspnea in these patients has been mainly attributed to cardiovascular determinants and isolated abnormalities of the respiratory system during exercise, neglecting the contribution of the control of the breathing system. The aim of this review is to provide a novel approach to the interpretation of dyspnea in patients with PH, focused on the impact of the control of the breathing system during exercise. Exercise through multiple mechanisms affects the (1) ventilatory demands, as dictated by respiratory center activity, (2) actual ventilation, and (3) metabolic hyperbola. In patients with PH, exertional dyspnea can be explained by exercise-induced alterations in these variables. Compared to healthy subjects, at a given CO2 production during exercise, ventilatory demands in patients with PH are higher due to metabolic acidosis (early reaching the anaerobic threshold), hypoxemia, and excessive upward movement of metabolic hyperbola owing to abnormal exercise response of dead space to tidal volume ratio. Simultaneously, dynamic hyperinflation and respiratory muscles weakness decreases the actual ventilation for a given respiratory center activity, creating a dissociation between demands and ventilation. Consequently, a progressive increase in ventilatory demands and respiratory center activity occurs during exercise. The forebrain projection of high respiratory center activity causes exertional dyspnea despite the relatively low ventilation and significant ventilatory reserve. This type of analysis suggests that the respiratory system is the main determinant of exertional dyspnea in patients with PH, with the cardiovascular system being an indirect contributor.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension in Greece: Data from the Hellenic Pulmonary Hypertension Registry.

Balloon pulmonary angioplasty (BPA) is a novel and promising treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA) and for those with persistent or recurrent pulmonary hypertension after PEA. We present the results of BPA procedures in CTEPH patients included in the Greek Pulmonary Hypertension Registry, evaluating the real-life efficacy and safety. We analyzed data from 180 BPA procedures (2−17/patient, mean 8 ± 4/patient, 1248 dilated vessels, 0−18/session). Significant improvements were observed in mean pulmonary arterial pressure (a reduction by 44%, p < 0.001), pulmonary vascular resistance (reduction by 60%, p < 0.001), and NT-proBNP (decrease by >70%, p: 0.003), while cardiac index improved modestly (9% increase, p = 0.143). We had 37 BPA-related non-fatal complications (20.6% in all interventions), predominantly including hemoptysis. Overall survival was 91%, 75% and 62% at 3, 4 and 5 years, respectively. Therefore, BPA may be a promising therapeutic option in patients with CTEPH in Greece.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Real-life Cretan asthma registry focused on severe asthma: On behalf of 'The Cretan registry of the use of Biologics in Severe Asthma'.

Asthma diagnosis and management remains a challenging task for the medical community. The aim of the present study was to present the functional and inflammatory profiles of patients with difficult-to-treat asthma in a real-life clinical setting referred to the specialized asthma clinic at the University Hospital of Heraklion. The registry included a cohort of 267 patients who were referred to the severe asthma clinic. Patients were assessed with emphasis on the history of allergies, nasal polyposis or other comorbidities. Blood testing for eosinophils counts and total and specific IgE, and pulmonary function tests were performed at baseline. The median age of patients with asthma was 55 years old, 68.5% were women and 58.3% were never smokers. The vast majority presented with late onset asthma (75.7%), whereas eight (3%) patients were on oral corticosteroids. The median number of exacerbations during the last 12 months was 1 (0-3). Furthermore, 50.7% of patients had a positive serum allergy test, the median eosinophil count was 300 (188-508.5) cells/µl of blood and median total IgE level was 117.5 (29.4-360.5) IU/ml. Patients were retrospectively grouped in the following categories: Group 1, mild-moderate asthma; group 2, patients prescribed a step 4 or 5 asthma therapy according to Global Initiative for Asthma; and group 3, patients on biologic agents. Group 1 had significantly higher FEV1% than groups 2 and 3 (93.4 vs. 79.9 and 79.4%, respectively; P<0.001). Finally, the median Asthma Control Questionnaire 7 (ACQ7) score was 1.14, with patients from groups 2 and 3 presenting higher ACQ7 scores compared with group 1 patients as expected (1.1 and 2.1 vs. 0.7, respectively; P<0.001). To the best of our knowledge, this was the first real-life asthma study in Crete that demonstrated that severe asthmatics predominantly have late-onset asthma with airflow obstruction and uncontrolled symptoms.

Epidemiology and initial management of pulmonary arterial hypertension: real-world data from the Hellenic pulmOnary hyPertension rEgistry (HOPE).

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.

Pulmonary Arterial Hypertension in Connective Tissue Disorders: The emerging role of screening and early diagnosis. A position paper for Greek Rheumatologists.

Pulmonary Arterial Hypertension is regarded as a devastating disease, complicating Connective Tissue Diseases. Although much progress has been achieved in the last 20 years, several unfulfilled needs in diagnosis and management of PAH in these patients may still be identified. After a systematic review of the literature and integrating results from the latest research articles, key clinical issues for the screening and diagnosis of Pulmonary Arterial Hypertension in Connective Tissue Disorder Patients and specifically Scleroderma patients are described in this article, allowing physicians to contribute to early diagnosis of patients with Scleroderma-associated Pulmonary Arterial Hypertension.

Does lung perfusion scintigraphy continue to have a role in the clinical management of patients suspected of pulmonary embolism in the CT pulmonary angiography era?

OBJECTIVE: Acute pulmonary embolism (PE) is a life-threatening disorder with high mortality. A prompt diagnosis and treatment is essential for reducing the mortality rate. The purpose of the study is to evaluate if lung perfusion scintigraphy (LPS) continues to have a role in the clinical management of patients suspected of pulmonary embolism in the CT pulmonary angiography (CTPA) era. METHODS: For this study, 1183 patients who had been subjected to LPS were retrospectively evaluated and classified into the following groups: A (positive LPS), B (negative LPS) and C (indeterminate LPS). Patients were further classified into A1 ('PE likely' and LPS-negative), B1 (PE unlikely and LPS-positive) and C1 (PE likely and indeterminate LPS) by combining the LPS findings and the clinical pretest probability (cpp). Subgroups A1, B1 and C1 underwent additional CTPA. RESULTS: Groups A, B, and C included 1086/1183, 69/1183 and 28/1183 patients, respectively. The proportion of patients with inconsistent cpp LPS findings who underwent additional CTPA was 106/1183 patients: subgroup A1 (n = 73), B1 (n = 21), and C1 (n = 12). In subgroup A1, CTPA was negative in 61/73, non-diagnostic in 12/73 and positive in 0/73 patients. In subgroup B1, CTPA excluded PE in 2/21, non-diagnostic in 3/21 and positive in 16/21 patients. In group C1, CTPA was negative in 8/12, positive in 2/12 and non-diagnostic in 2/12 patients. CONCLUSION: In the CTPA era, LPS continues to have a role in the clinical management of patients suspected of PE.

New respiratory symptoms and lung imaging findings in a woman with polymyositis.

Can you identify the cause of the acute respiratory failure in this patient with a history of polymyositis? http://ow.ly/jeDO30jLX5R.

Evaluation of acid-base status in patients admitted to ED-physicochemical vs traditional approaches.

BACKGROUND: The aim of this study is to evaluate the value of physicochemical, base excess (BE), and plasma bicarbonate concentration ([HCO3(-)]) approaches on the assessment of acid-base status in patients presented to the emergency department (ED). METHODS: Upon presentation at ED, patients whose arterial blood was deemed in need of analysis were studied. Arterial blood gases, serum electrolytes, and proteins were measured and used to derive [HCO3(-)], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG) and SIG corrected for water excess/deficit (SIGcor). In each patient the acid-base status was evaluated using the BE, [HCO3(-)], and physicochemical approaches. RESULTS: A total of 365 patients were studied. Compared with BE (n = 202) and [HCO3(-)] (n = 151), physicochemical approach (n = 279) identified significantly more patients with metabolic acid-base disturbances (P < .0001). Significantly fewer patients with unmeasured anions acidosis were identified with AGadj than with SIGcor (164 vs 230; P < .0001). On the basis of BE, 75 patients had normal acid-base balance, and 65 (87%) of them exhibited at least 1 hidden acid-base disturbance, identified by the physicochemical approach. The corresponding values with [HCO3(-)] approach were 108 and 95 (88%) patients. When patients with high AGadj were excluded, 44 patients with BE and 67 with [HCO3(-)] approach had normal acid-base status, and most of them exhibited at least 1 acid-base disturbance with the physicochemical approach, whereas 12 and 21 patients, respectively, had high SIGcor. CONCLUSION: Compared with the BE and [HCO3(-)] methods, the physicochemical approach has a better diagnostic accuracy to identify metabolic acid-base disturbances.

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation.

BACKGROUND: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation. METHODS: Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits. RESULTS: Sputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation. CONCLUSIONS: Only nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.

Decreased sputum mature dendritic cells in healthy smokers and patients with chronic obstructive pulmonary disease.

BACKGROUND: Asthmatics who smoke have decreased pulmonary mature dendritic cells (DCs). Chronic obstructive pulmonary disease (COPD) patients have an increased amount of pulmonary immature DCs. We hypothesized that healthy smokers and patients with COPD have decreased pulmonary mature DCs. METHODS: We identified sputum DCs expressing the maturation markers CD83 and DC-lysosome associated membrane protein (DC-LAMP) and DC subpopulations (i.e. myeloid and plasmacytoid DCs) by flow cytometry in healthy smokers before they entered a smoking cessation trial (n = 30), in the same smokers after 6 months of smoking cessation (n = 11) and in COPD patients (n = 28, 14 current and 14 ex-smokers). 12 healthy never-smokers served as controls. DC numbers were expressed as percentage of total sputum CD45(+) leukocytes. RESULTS: CD83(+) and DC-LAMP(+) mature DCs were decreased in healthy smokers before they ceased smoking compared to after (p = 0.003 and p = 0.049, respectively) and in smokers before smoking cessation compared to never-smokers (p = 0.027 and p = 0.028, respectively). COPD patients, both current and ex-smokers, showed decreased CD83(+) mature DCs compared to never-smokers and smokers after cessation (p = 0.042 and p = 0.004, respectively). CONCLUSIONS: Cigarette smoking and COPD per se are associated with a decrease in pulmonary mature DCs. We speculate that this reduction is involved in the immunopathogenesis of smoking-related respiratory disorders, such as COPD.

Maintained smoking cessation for 6 months equilibrates the percentage of sputum CD8+ lymphocyte cells with that of nonsmokers.

Little is known about the longitudinal effects of smoking cessation on sputum inflammatory cells. We aimed to investigate the changes in sputum inflammatory cells and T-lymphocyte subpopulations after 6 and 12 months smoking cessation. Induced sputum was obtained from 68 healthy smokers before and after 6 months (n = 21) and 1 year (n = 14) smoking cessation and from ten healthy never-smokers. Inflammatory cells were identified by morphology and T-lymphocyte subpopulations by flow cytometry. Sputum macrophages were decreased after 12 months of smoking cessation in comparison to baseline, while neutrophils increased. Moreover, CD8+ T-cells were decreased in smokers before smoking cessation compared to never-smokers and increased in smokers after 6 months of smoking cessation in comparison to baseline; result that was maintained after 1 year of smoking cessation. These novel findings indicate that smoking cessation can equilibrate certain inflammatory cells of smokers with those of nonsmokers, within 6 months of smoking cessation.

Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast cancer and bloody vaginal discharge.

BACKGROUND: Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries. CASE PRESENTATION: A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully. CONCLUSION: Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.

Vascular-specific growth factor mRNA levels in the human diaphragm.

BACKGROUND: Angiogenesis is an adaptation mechanism of skeletal muscles to increased load. Animal data have shown increased vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in the diaphragm as a result of increased minute ventilation, but there are no data concerning the human diaphragm. OBJECTIVES: The purpose of this study was to investigate the VEGF, bFGF, TGF-beta(1) mRNA levels in the human diaphragm of normal subjects and patients with altered respiratory mechanics. METHODS: We studied 9 patients with chronic obstructive pulmonary disease (COPD), 4 obese patients and 12 controls. We performed multiplex semiquantitative reverse transcription polymerase chain reaction to determine the VEGF, bFGF and TGF-beta(1) mRNA levels in specimens taken from their diaphragm. RESULTS: VEGF mRNA levels were 18% higher in COPD patients compared with controls (p = 0.04), while for the obese patients, these levels were not statistically significantly different. bFGF and TGF-beta(1) mRNA levels in COPD patients or obese individuals compared with controls did not differ significantly either. CONCLUSIONS: The results of our study showed that TGF-beta(1), VEGF and bFGF mRNA was detected in the human diaphragm. The VEGF levels were higher in COPD patients than in normal subjects. This upregulation of VEGF may suggest an enhancement of angiogenesis in the diaphragm in COPD patients.

Peripheral arterial embolism due to a left ventricular diverticulum in a young adult.

A 32-year-old man was admitted to the emergency department of our hospital after experiencing a peripheral arterial embolism. Investigation of the possible embolic sources in an otherwise asymptomatic patient revealed the existence of a left ventricular diverticulum. The left ventricular diverticulum is a rare congenital anomaly, either isolated or as a part of a syndrome including other congenital malformations. The treatment of choice, especially in symptomatic patients, is surgical resection, while in asymptomatic patients anticoagulation therapy is indicated.