Search

Background: Severe pneumonia caused by coronavirus disease 2019 (COVID‐19) is char‐ acterized by inflammatory lung injury, progressive parenchymal stiffening and consolidation, alveolar and airway collapse, altered vascular permeability, diffuse alveolar damage, and surfactant deficiency. COVID‐19 causes both pneumonia and acute respiratory distress syndrome (COVID‐19 ARDS). COVID‐19 ARDS is characterized by severe refractory hypoxemia and high mortality. De‐ spite extensive research, the treatment of COVID‐19 ARDS is far from satisfactory. Some treatments are recommended for exhibiting some clinically positive impacts on COVID‐19 patients although there are already several drugs in clinical trials, some of which are already demonstrating promising results in addressing COVID‐19. Few studies have demonstrated beneficial effects in non‐COVID‐ 19 ARDS treatment of exogenous surfactant, and there is no evidence‐based, proven method for the procedure of surfactant administration. Aim: The aim of this work is to underline the key role of ATII cells and reduced surfactant levels in COVID-19 ARDS and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS, providing insight for future research. Methods: In this article, we describe and support via the literature the decision to administer large volumes of surfactant to two patients via bronchoalveolar lavage to maximize its distribution in the respira‐ tory tract. Results: In this study, we report on two cases of COVID‐19 ARDS in patients who have been successfully treated with diluted surfactants by bronchoalveolar lavage, followed by a low‐ dose bolus of surfactant. Conclusion: Combining the administration of diluted, exogenous pulmo‐ nary surfactant via bronchoalveolar lavage along with the standard therapy for SARS‐COV‐2‐induced ARDS may be a promising way of improving the management of ARDS.

ObjectiveThe coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19.Materials and methodsThe present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019.ResultsAmong 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (pConclusionA cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by the presence of generalized vasculopathy and tissue fibrosis. Collagen vascular disorder in SSc is due to fibroblast and endothelial cell dysfunctions. This leads to collagen overproduction, vascular impairment and immune system abnormalities and, in the last stage, multi-organ damage. Thus, to avoid organ damage, which has a poor prognosis, all patients should be carefully evaluated and followed. This is particularly important in the initial disease phase, so as to facilitate early identification of any organ involvement and to allow for appropriate therapy. Pulmonary disease in SSc mainly involves interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). High-resolution computed tomography (HRCT) and pulmonary function tests (PFT) have been proposed to monitor parenchymal damage. Although transthoracic echocardiography is the most commonly used screening tool for PAH in SSc patients, definitive diagnosis necessitates confirmation by right heart catheterization (RHC). Moreover, some studies have demonstrated that nailfold videocapillaroscopy (NVC) provides an accurate evaluation of the microvascular damage in SSc and is able to predict internal organ involvement, such as lung impairment. This review provides an overview of the correlation between lung damage and microvascular involvement in SSc patients.

Questo libro non è un manuale di broncoscopia e neppure una guida alla scelta del miglior broncoscopio per un determinato paziente. Questo libro vuole essere, invece, un aiuto per motivare quando, come e perchè acquistare e utilizzare broncoscopi monouso. E' stato scritto per pneumologi che fanno uso quotidiano della broncoscopia e hanno vissuto l'esperienza della pandemia COVID-19 in prima linea. Il libro può essere utilizzato da chiunque sia coinvolto sul tema. vengono trattati nello specifico i temi dell'uso dei broncoscopi durante la pandemia COVID-19, la problematica delle infezioni ospedalieri e correlate all'assistenza (ICA), il Piano PNCAR del Ministero della salute, l'utilizzo del monouso nella pratica clinica, il reprocessing, le evidenze economiche (es. costo-efficacia) e l'impatto ambientale e le considerazioni della green economy.

We aimed at evaluating not the diagnostic yield of BAL in COVID-19, but the agreement between negative upper respiratory tract swabs and BAL to exclude COVID-19, stressing that BAL is likely negative if swabs and chest CT are concordantly negative.

The echocardiographic estimation of right atrial pressure (RAP) is based on the size and inspiratory collapse of the inferior vena cava (IVC). However, this method has proven to have limits of reliability. The aim of this study is to assess feasibility and accuracy of a new semi-automated approach to estimate RAP. Standard acquired echocardiographic images were processed with a semi-automated technique. Indexes related to the collapsibility of the vessel during inspiration (Caval Index, CI) and new indexes of pulsatility, obtained considering only the stimulation due to either respiration (Respiratory Caval Index, RCI) or heartbeats (Cardiac Caval Index, CCI) were derived. Binary Tree Models (BTM) were then developed to estimate either 3 or 5 RAP classes (BTM3 and BTM5) using indexes estimated by the semi-automated technique. These BTMs were compared with two standard estimation (SE) echocardiographic methods, indicated as A and B, distinguishing among 3 and 5 RAP classes, respectively. Direct RAP measurements obtained during a right heart catheterization (RHC) were used as reference. 62 consecutive ‘all-comers’ patients that had a RHC were enrolled; 13 patients were excluded for technical reasons. Therefore 49 patients were included in this study (mean age 62.2 ± 15.2 years, 75.5% pulmonary hypertension, 34.7% severe left ventricular dysfunction and 51% right ventricular dysfunction). The SE methods showed poor accuracy for RAP estimation (method A: misclassification error, ME = 51%, R2 = 0.22; method B: ME = 69%, R2 = 0.26). Instead, the new semi-automated methods BTM3 and BTM5 have higher accuracy (ME = 14%, R2 = 0.47 and ME = 22%, R2 = 0.61, respectively). In conclusion, a multi-parametric approach using IVC indexes extracted by the semi-automated approach is a promising tool for a more accurate estimation of RAP.

Given the strong agreement between negative upper respiratory swabs and BAL, this study suggests that BAL has a limited role in the diagnosis of COVID-19 if thoracic imaging and upper respiratory swabs are concordantly negativehttps://bit.ly/3gpBC75

The diagnosis and classification of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential to improve the prognosis of systemic sclerosis (SSc) patients. The risk-stratification of disease severity and follow-up requires a multidisciplinary approach, integrating high-resolution computed tomography (HRTC) of the lung, pulmonary function tests (PFT), along with clinical and symptomatic evaluations. The use of HRCT in detecting SSc-ILD is not so much based on a definitive validation, but rather reflects the widespread clinician recognition of dissatisfaction with other modalities. However, due to the heterogeneity of SSc-ILD and the potential absence of symptoms in early or mild disease, it is prudent to consider as many parameters as possible in the assessment and monitoring of newly diagnosed patients. An early diagnosis meets the primary goal, i.e., the prevention of disease progression. The current first line treatment regimens are mainly centered on immunosuppressive therapy. This review assesses the role HRCT plays in optimizing care and improving clinical outcomes in SSc-ILD patients.

Background Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD. Methods After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter. Results The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo –1.4 WU; 95% confidence interval, ≤ –0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups. Conclusions This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.

AIMS: The study aimed at evaluating the reliability and reproducibility of various noninvasive echocardiographic techniques for the estimation of the main hemodynamic parameters in clinical practice. METHODS: A total of 84 patients with a generic indication of right heart catheterization (RHC) executed a transthoracic echocardiography shortly before or after the RHC. All the parameters necessary for a noninvasive hemodynamic evaluation of right atrial pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, pulmonary vascular resistance and cardiac output were acquired and the agreement with the invasive measures was evaluated by a Bland-Altman analysis. RESULTS: Noninvasive evaluation of right atrial pressure showed a moderate and low correlation with RHC using inferior vena cava parameters (r = 0.517) and tricuspid E/E' ratio (sensitivity 0.23, specificity 0.72), respectively. PAPs estimation from the tricuspid regurgitation peak velocity had a good correlation (r = 0.836) and feasibility (82.1%), as well as PAPm from tricuspid regurgitation mean gradient (r = 0.78, applicability 72.6%) and from pulmonary acceleration time (sensitivity 0.85, specificity 0.5, applicability 92.9%). Pulmonary capillary wedge pressure multiparametric evaluation, as suggested by the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations, showed a good correlation (sensitivity 0.96, specificity 0.59). The noninvasive evaluation of pulmonary vascular resistance and cardiac output did not prove to be clinically accurate. CONCLUSION: Various hemodynamic parameters can be adequately estimated with noninvasive methods. In particular, a multiparametric approach for the evaluation of left ventricle filling pressures is advisable and the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations are reliable even in a heterogeneous population with a significant quota of precapillary pulmonary hypertension.

C1q is the first recognition subcomponent of the complement classical pathway, which acts towards the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, including their involvement in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumour by encouraging their adhesion, migration and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of C1q in the microenvironment of malignant pleuric mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid via its globular domain. C1q bound to hyaluronic acid was able to induce adhesion and proliferation of mesothelioma cells via enhancement of ERK1/2, SAPK/JNK and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organisation of the globular domain, we demonstrated that C1q may bind to hyaluronic acid through ghA module, whereas it may interact with human mesothelioma cells through the ghC. In conclusion, C1q highly expressed in MPM binds to hyaluronic acid and enhances the tumour growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.

Congenital central hypoventilation syndrome (CCHS) is defined as failure of the chemical (autonomic) control of breathing causing alveolar hypoventilation in the absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions. Hypoventilation is predominant in non-rapid-eye-movement sleep, during which breathing is primarily under chemical control. Failure of the central integration of chemosensory inputs is proposed as the putative defect. A genetic basis for CCHS is supported by lines of evidence. In some diseases of the central nervous system there is more or less complete depression of the cough reflex, whereas spontaneous ventilation is generally preserved. Little is known regarding cough in CCHS patients. Parents consistently report that their children cough ‘normally’ during airway infections; in contrast, experimental lines of evidence suggest that CCHS children lack a cough response following inhalation of a tussigenic agent. Although several factors may account for the discrepancy, the possibility of a weakened or even absent cough reflex remains to be fully ascertained. Conceivably, a defective cough reflex, in conjunction with the well established lack of perception of respiratory discomfort, might result in an increased risk of potentially serious respiratory complications in CCHS patients.

Congenital central hypoventilation syndrome (CCHS) is a genetic disorder mainly characterized by failure of automatic control of breathing, causing alveolar hypoventilation. Little is known regarding cough in CCHS. Parental reports indicate that patients cough normally during airway infections; however, previous studies have demonstrated no cough response to fog inhalation.To evaluate the sensory and motor components of cough, respiratory sensations, and changes in ventilation evoked by fog inhalation in children with CCHS and in sex- and age-matched control subjects.Cough threshold was measured and cough intensity was indexed in terms of cough peak expiratory flow and integrated abdominal electromyographic activity. The pattern of breathing was recorded by inductive plethysmography. Respiratory sensations were also investigated.All control subjects and six of seven patients coughed in response to fog inhalation. The seventh coughed with citric acid aerosol inhalation. Cough threshold values were similar in control subjects (range, 0.40-2.22 ml/min) and patients (range, 0.40-3.26 ml/min). Mean values of cough peak expiratory flow and of integrated abdominal electromyographic activity-related variables during coughing were also similar and corresponded to 80% of those recorded during maximum voluntary cough. Cough appearance was preceded by respiratory sensations and increases (P0.01) in ventilation in the control subjects but not in the patients.Children with CCHS have normal cough threshold and motor responses to fog inhalation. However, the lack of respiratory sensations and the likely related ventilatory changes typically elicited by tussigenic fog concentrations suggest a neural sensory deficit that may increase the risk of respiratory disease in these patients.

For inhaled medications, bioequivalence testing is becoming increasingly important owing to the availability of many inhalation devices. We evaluated agreement between the Finney bioassay and the Emax model in the assessment of bioequivalence of salbutamol administered via a metered-dose inhaler with a spacer (pMDI+ Volumatic) or via a dry-powder inhaler (Diskus) in asthmatic patients with methacholine-induced bronchoconstriction. Eighteen patients inhaled methacholine until FEV 1 decreased by approximately 35% of control. Following inhalation of placebo, 200 and 400 mcg salbutamol through the pMDI+ Volumatic or the Diskus, changes in FEV 1 were repeatedly measured over a 60-min observation period. Bioequivalence of salbutamol administered via the two inhalation devices was assessed by calculating the relative potency of each device by using the Finney 2-by-2 parallel regression analysis and the non-linear, Emax model. Agreement between these methods in calculating relative potency was evaluated by using the Bland-Altman method. After salbutamol FEV 1 values were similar irrespective of the device employed, and greater (P0.01) than those after placebo. However, assessment of relative potencies obtained with both the Finney (1.97, 90% CI 1.62-2.32) and the Emax (2.25, 90% CI 1.90-2.60) methods revealed that twice the salbutamol dose was needed to reverse methacholine-induced bronchoconstriction when the drug was inhaled via the Diskus than via the pMDI+ Volumatic. The mean difference in relative potency (-0.28, 90% CI -0.001 to -0.56) calculated with both methods did not significantly differ from zero, and none of the individual differences exceeded the limits of agreement. The Finney and the Emax methods provide comparable results in the evaluation of bioequivalence of different salbutamol formulations. The pMDI+ Volumatic is twice as efficient as the Diskus in lung delivery of salbutamol in asthma patients.

Airway receptors mediate cough and ventilatory adjustments. Simultaneous assessment of cough sensory-motor components and changes in breathing pattern may provide insights into the receptor(s) prevailingly stimulated by inhaled irritants. Nineteen subjects inhaled capsaicin and fog up to threshold concentrations for cough. Cough intensity, respiratory sensations and changes in breathing pattern induced by the two irritants were compared. Capsaicin and fog cough threshold values did not correlate. Coughing induced by both agents was preceded by qualitatively similar sensations and by significant increases in minute ventilation and respiratory drive due to selective increases in tidal volume (P

Aims To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. Methods Eighteen patients inhaled methacholine (MCh) until FEV1 decreased by 35% of control. Following administration of placebo, 200 µg salbutamol or 400 µg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV1 and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. Results For all functional variables, recovery times were significantly (P

Aims This study aimed at evaluating changes in airway patency, lung volumes and perception of breathing discomfort intensity following salbutamol administration via the Diskus dry-powder inhaler (DPI) or a pressurized metered-dose inhaler with the Volumatic valved holding chamber (pMDI + Volumatic) in asthmatic patients with methacholine-induced bronchoconstriction. Methods On six different study days, 18 patients inhaled methacholine until forced expiratory volume in 1 s (FEV1) decreased by approximately 35% of baseline. Following placebo, 200 and 400 µg of salbutamol through the pMDI + Volumatic or the Diskus, changes in FEV1, volume-adjusted mean forced expiratory flow from 25 to 75% of the forced vital capacity (isoFEF25−75), lung volumes and breathing discomfort intensity, assessed by visual analogue scale (VAS) score, were repeatedly measured over a 60-min observation period. Results Induced bronchoconstriction was accompanied by obvious reductions in lung volumes and increases in VAS score. After salbutamol administration, FEV1 and VAS score changes were similar in all experimental conditions. However, following 400 µg salbutamol via pMDI + Volumatic, isoFEF25−75 values increased up to 4.48 l s−1 (95% confidence interval 4.06, 4.90), a significantly (P