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1.
Histopathology ; 83(2): 229-241, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37102989

ABSTRACT

AIMS: While there is partial evidence of lung lesions in patients suffering from long COVID there are substantial concerns about lung remodelling sequelae after COVID-19 pneumonia. The aim of the present retrospective comparative study was to ascertain morphological features in lung samples from patients undergoing tumour resection several months after SARS-CoV-2 infection. METHODS AND RESULTS: The severity of several lesions with a major focus on the vascular bed was analysed in 2 tumour-distant lung fragments of 41 cases: 21 SARS-CoV-2 (+) lung tumour (LT) patients and 20 SARS-CoV-2 (-) LT patients. A systematic evaluation of several lesions was carried out by combining their scores into a grade of I-III. Tissue SARS-CoV-2 genomic/subgenomic transcripts were also investigated. Morphological findings were compared with clinical, laboratory and radiological data. SARS-CoV-2 (+) LT patients with previous pneumonia showed more severe parenchymal and vascular lesions than those found in SARS-CoV-2 (+) LT patients without pneumonia and SARS-CoV-2 (-) LT patients, mainly when combined scores were used. SARS-CoV-2 viral transcripts were not detected in any sample. SARS-CoV-2 (+) LT patients with pneumonia showed a significantly higher radiological global injury score. No other associations were found between morphological lesions and clinical data. CONCLUSIONS: To our knowledge, this is the first study that, after a granular evaluation of tissue parameters, detected several changes in lungs from patients undergoing tumour resection after SARS-CoV-2 infection. These lesions, in particular vascular remodelling, could have an important impact overall on the future management of these frail patients.


Subject(s)
COVID-19 , Lung Neoplasms , Humans , SARS-CoV-2 , Post-Acute COVID-19 Syndrome , Retrospective Studies , Lung
2.
ERJ Open Res ; 9(2)2023 Mar.
Article in English | MEDLINE | ID: mdl-36949965

ABSTRACT

Introduction: Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy. Methods: A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis. Results: 14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47-61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake (V'O2 peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy. Conclusion: CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy.

3.
J Pers Med ; 14(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38248740

ABSTRACT

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99-6.8) and 5.4-fold (p = 0.002; CI 1.9-16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

5.
ERJ Open Res ; 8(3)2022 Jul.
Article in English | MEDLINE | ID: mdl-36171986

ABSTRACT

This study of the eosinophil cationic protein (ECP) as predictor of clinical response to biological therapy in severe asthma found that ECP is not useful in unselected patients but may have a role in those not exposed to oral corticosteroids. https://bit.ly/398RwEk.

6.
Expert Rev Respir Med ; 16(6): 623-635, 2022 06.
Article in English | MEDLINE | ID: mdl-35722753

ABSTRACT

INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), static and dynamic hyperinflation, together with expiratory flow limitation and gas exchange abnormalities, is one of the major causes of dyspnea, decreased exercise performance and ventilatory failure. An increase in functional residual capacity (FRC) is accompanied by a decrease in inspiratory capacity (IC), which is a volume readily available, repeatable, and simple to measure with any spirometer. Changes in IC and FRC after bronchodilation, contrary to changes in FEV1, have been closely associated with improvements in dyspnea and exercise performance. We systematically searched PubMed and Embase databases for clinical trials that assessed the effects of dual bronchodilation on inspiratory capacity in patients with COPD. AREAS COVERED: Despite their pivotal role in COPD, IC and static volumes have rarely been considered as primary outcomes in randomized clinical trials assessing the efficacy of bronchodilators. Available studies on dual bronchodilation have shown a significant and persistent positive impact on IC focusing mainly on patients with moderate-to-severe COPD, whereas dynamic hyperinflation is also present at milder disease stages. EXPERT OPINION: This narrative review discusses the pathophysiological and clinical importance of measuring IC in patients with COPD and how IC can be modified by maximizing bronchodilation combining long-acting muscarinic antagonists and long-acting ß2 agonists.


Subject(s)
Muscarinic Antagonists , Pulmonary Disease, Chronic Obstructive , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Dyspnea , Forced Expiratory Volume , Humans , Inspiratory Capacity/physiology , Muscarinic Antagonists/pharmacology , Muscarinic Antagonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy
7.
Eur J Surg Oncol ; 48(9): 1929-1936, 2022 09.
Article in English | MEDLINE | ID: mdl-35246347

ABSTRACT

BACKGROUND: The surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels. METHODS: 362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients. RESULTS: Overall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p < 0.001 and 3.0HR p < 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p < 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p < 0.05 and 1.6HR p < 0.05). CONCLUSIONS: Surgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Neoplasm Staging , Pneumonectomy/methods , Retrospective Studies , Vena Cava, Superior/pathology , Vena Cava, Superior/surgery
8.
Interact Cardiovasc Thorac Surg ; 34(2): 255-257, 2022 01 18.
Article in English | MEDLINE | ID: mdl-34480559

ABSTRACT

Pulmonary sequestrations are rare congenital malformations. They are often located in the lower lobes, and they are supplied by an aberrant systemic vessel arising from the thoracic aorta or abdominal arteries. These pulmonary malformations are divided into intra- and extralobar sequestrations, depending on the respective lack or presence of an independent pleural covering. Pulmonary sequestration can be asymptomatic or lead to recurrent pulmonary infections. The goal of this study was to analyse the feasibility and safety of a hybrid sequential approach. We report a small series of intralobar pulmonary sequestrations, from November 2017 to December 2018, successfully treated with a hybrid minimally invasive approach consisting of endovascular embolization of the aberrant arterial branch followed by video-assisted thoracoscopic lobectomy the day after. Thoracic pain following endovascular embolization was noted in all cases. Patients were discharged early in the absence of major postoperative complications. Prolonged air leak was observed in only 1 case. Despite the presence of sequestration-related pulmonary inflammation, in our experience, hybrid treatment for intralobar pulmonary sequestration is a safe and reproducible approach in terms of postoperative complications and hospital stay.


Subject(s)
Bronchopulmonary Sequestration , Embolization, Therapeutic , Bronchopulmonary Sequestration/diagnostic imaging , Bronchopulmonary Sequestration/surgery , Embolization, Therapeutic/adverse effects , Humans , Lung/surgery , Thoracic Surgery, Video-Assisted/adverse effects , Tomography, X-Ray Computed
9.
Pharmacol Res ; 173: 105915, 2021 11.
Article in English | MEDLINE | ID: mdl-34571145

ABSTRACT

If short acting ß2-agonists and muscarinic antagonists (SABA/SAMA) may have proarrhythmic effects during acute COPD exacerbations (AECOPD) is still unknown. The primary objective of the study was to investigate the incidence of new onset arrhythmias in hospitalized patients shifted to SABA/SAMA during an AECOPD compared with continuing chronic inhaled therapy. Secondary objectives were to assess the clinical characteristics of patients shifted to SABA/SAMA and risk factors for arrhythmia. This was a retrospective, observational, study enrolling consecutive patients hospitalized with an AECOPD. Incidence of arrhythmias was obtained reviewing digital records. Patients with chronic arrhythmias or home-treated with SABA/SAMA were excluded. 235 patients (63.8% males) were included, and 10/182 patients shifted to SABA/SAMA experienced arrhythmias, while no events were observed in patients on chronic inhaled therapy (p = 0.122). Shifted patients had a more severe AECOPD and history of paroxysmal atrial fibrillation was an independent risk factor for arrhythmia (OR 14.010, IC95%: 2.983-65.800; p = 0.001). In conclusion, shifting patients to SABA/SAMA appears not to increase the risk for arrhythmia during severe AECOPD. However, the pharmacological approach in patients with a history of paroxysmal arrhythmia should be carefully evaluated and monitored.


Subject(s)
Adrenergic beta-2 Receptor Agonists/administration & dosage , Arrhythmias, Cardiac/epidemiology , Bronchodilator Agents/administration & dosage , Muscarinic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Aged , Aged, 80 and over , Drug Substitution , Female , Hospitalization , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Retrospective Studies , Risk Factors
10.
J Crit Care ; 65: 1-8, 2021 10.
Article in English | MEDLINE | ID: mdl-34052780

ABSTRACT

INTRODUCTION AND AIM: Non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) have been widely employed to treat acute respiratory failure secondary to COVID-19 pneumonia, but their role in terms of efficacy and safety are still debated. The aim of this review was to analyse mortality and intubation rates in COVID-19 patients treated with NIV/CPAP. METHODS: Rapid review methodology was applied to include all the studies published since December-2019 until November-2020 with available data on in-hospital mortality in COVID-19 patients treated with NIV or CPAP. RESULTS: 23 manuscripts were included (4776 patients, 66% males, 46% with hypertension). 46% of patients received non-invasive respiratory support, of which 48.4% with CPAP, 46% with NIV, and 4% with either CPAP or NIV. Non-invasive respiratory support failed in 47.7% of patients, of which 26.5% were intubated and 40.9% died. In-hospital mortality was higher in patients treated with NIV compared with CPAP (35.1% vs. 22.2%). Complications were under-reported, but mostly not related to CPAP/NIV treatment. CONCLUSION: CPAP and NIV appear equally and frequently applied in patients with COVID-19 pneumonia, but associated with high mortality. Robust evidence is urgently needed to confirm the clinical efficacy of non-invasive respiratory support in COVID-19-related ARDS.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Distress Syndrome , Continuous Positive Airway Pressure , Female , Humans , Male , SARS-CoV-2
11.
J Clin Med ; 10(5)2021 Mar 02.
Article in English | MEDLINE | ID: mdl-33801455

ABSTRACT

Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April-May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (ß -18.675; 95%CI, -28.373--9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.

12.
Respir Med ; 178: 106323, 2021 03.
Article in English | MEDLINE | ID: mdl-33545499

ABSTRACT

BACKGROUND: The therapeutic approach to COVID-19 and healthcare system preparedness improved during 2020. We compared characteristics and outcomes of hospitalized COVID-19 patients during the first 28 days of the March and October pandemic waves in Milan, Italy. MATERIAL AND METHODS: A prospective, observational study enrolling adult patients hospitalized with COVID-19 pneumonia during March 7-April 4 (1st period) and October 15-November 12 (2nd period). During the 1st period hydroxychloroquine, lopinavir/ritonavir and therapeutic enoxaparin when thrombosis was confirmed were administered; systemic corticosteroids were given in case of severe pneumonia. During the 2nd period dexamethasone, methylprednisolone, remdesivir, thromboprophylaxis or anticoagulation were administered according to international recommendations. Patients with respiratory distress on oxygen masks initiated CPAP. Outcomes were: length of hospital stay, all-cause in-hospital mortality and need for intubation. RESULTS: We included 70 patients (75% males) during the 1st and 76 patients (51% males, p = 0.522) during the 2nd period. Prevalence of severe respiratory failure (30% vs. 12%, p = 0.006), and D-dimer >3000 FEU (34% vs. 15%, P = 0.012) were reduced during the 2nd period, while anticoagulation and corticosteroids were more frequently administered (both p < 0.01). Mortality and time to referral were also reduced (39.4% vs. 22.4%, p = 0.019 and 6 vs. 5 days, p = 0.014), while need for intubation didn't change. Hospitalization length was comparable, but the proportion of patients discharged home was higher during the 2nd period (28.2% vs. 55.4%, p = 0.001). CONCLUSIONS: Changing treatment paradigms and early referral might have reduced mortality in COVID-19 patients. The effects of specific therapeutic regimens needs further confirmation in future clinical studies.


Subject(s)
COVID-19/therapy , Hospitalization , Respiratory Therapy , Adult , Aged , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Female , Hospital Mortality , Humans , Italy , Length of Stay , Male , Middle Aged , Prospective Studies , Seasons , Survival Rate
14.
BMJ Open ; 10(10): e043651, 2020 10 10.
Article in English | MEDLINE | ID: mdl-33040020

ABSTRACT

OBJECTIVES: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood. DESIGN: Observational, prospective, multicentre study. SETTING: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards. PARTICIPANTS: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded. INTERVENTIONS: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay. RESULTS: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04). CONCLUSIONS: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality. TRIAL REGISTRATION NUMBER: NCT04307459.


Subject(s)
Coronavirus Infections/pathology , Hospital Mortality , Hospitalization , Oxygen/blood , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/etiology , Severe Acute Respiratory Syndrome/etiology , Severity of Illness Index , Aged , Betacoronavirus , Blood Gas Analysis , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , Hospitals , Humans , Hypoxia , Intensive Care Units , Italy/epidemiology , Lung/metabolism , Lung/pathology , Lung/virology , Male , Middle Aged , Pandemics , Partial Pressure , Pneumonia, Viral/metabolism , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prospective Studies , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology
15.
J Thorac Dis ; 12(6): 3363-3368, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32642261

ABSTRACT

To date, pulmonary function tests (PFTs) are part of consolidated standard operating procedures in thoracic surgery. PFTs are usually used to assess the pre-operative risk, post-operative outcomes and complications after pulmonary resections. The only functional parameter used in common practice is the forced expiratory volume in one second (FEV1). However, the FEV1 alone poorly reflects lung pathophysiology, especially in patients with pre-operative emphysema and airflow obstruction; moreover, the predictive power of spirometric parameters in guiding the surgical approach in terms of the extension of the excision is currently unknown. In the present critical overview, we report and discuss the results of four studies that compared pre and post-surgery FEV1 and forced vital capacity (FVC) in patients undergoing lobectomy or segmentectomy, highlighting the critical aspects of spirometry in lung surgery and suggesting new approaches for the interpretation of pulmonary mechanics in patients undergoing major or minor parenchymal resections. Overall, the literature on the topic is limited to spirometric parameters, and post-surgical function loss and the consequent recovery are often analysed in inhomogeneous study samples, with varying respiratory comorbidities and functional phenotypes. We underline the role of static lung volumes in the patients' initial assessment. In fact, they tend to decrease in patients with emphysema that undergo a lobectomy, followed by a decrease in lung compliance; some of these patients experience also an increase in closing volume, a condition that worsens the stresses implicated in lung ventilation and promotes the damage to the remaining airways. Spirometric data should be therefore always associated to body-plethysmography and indexes of ventilation distribution, to improve the evaluation of the functional characteristics in patients undergoing lung surgery. Prospective studies are needed to establish the relationship and long-term consequences of different surgical approaches in terms of lung mechanics and functional loss.

16.
Surg Today ; 50(2): 114-122, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31493198

ABSTRACT

PURPOSE: Bronchopleural fistula (BPF) is a potentially fatal complication of pneumonectomy. We analyze its occurrence rate, risk factors, and the methods used for its prevention. METHODS: We reviewed the medical records of patients who underwent pneumonectomy at our Institution between January, 1990 and March, 2016. The risk factors for postoperative BPF were analyzed by univariate analysis and multiple logistic regression. RESULTS: Over the study period, 511 patients underwent pneumonectomy for non-small cell lung cancer (NSCLC) and had the bronchus closed by manual suturing. BPF developed in 23 patients (4.5%). Multiple logistic regression identified no coverage of the bronchial stump, right-sided pneumonectomy, residual tumor in the bronchial stump, postoperative ventilatory support, and completion pneumonectomy, as independent risk factors for BPF. The cumulative rate of BPF decreased significantly over time from 18% between 1990 and 1995 to 1% between 2011 and 2016 (p < 0.001). Concurrently, the data of several patients showed a significant positive trend over time, including bronchial stump coverage (BSC). DISCUSSION: Several known risk factors for BPF were confirmed. The more frequent usage of tissue flaps for coverage of the bronchial stump may have contributed to the reduction in the rate of postoperative BPF over time.


Subject(s)
Bronchi/surgery , Bronchial Fistula/etiology , Fistula/etiology , Pleural Diseases/etiology , Pneumonectomy , Postoperative Complications/epidemiology , Bronchial Fistula/epidemiology , Carcinoma, Non-Small-Cell Lung/surgery , Fistula/epidemiology , Humans , Lung Neoplasms/surgery , Pleural Diseases/epidemiology , Risk Factors
17.
Article in English | MEDLINE | ID: mdl-30733864

ABSTRACT

BACKGROUND: The analysis of microbiome in respiratory samples is a topic of great interest in chronic respiratory diseases. The method used to prepare sputum samples for microbiome analysis is very heterogeneous. The selection of the most suitable methodology for DNA extraction is fundamental to have the most representative data. The objective of this study was to compare different conditions for DNA extraction from sputum in adult patients with bronchiectasis. METHODS: Five sputum samples from bronchiectasis patients were collected at the Policlinico Hospital in Milan, Italy. Eighteen conditions for DNA extraction were compared, including two enzyme-based (Roche and Zymo) and one beads-based (Mobio) technique. These techniques were tested with/without Dithiothreitol (DTT) and with/without lysostaphin (0.18 and 0.36 mg/mL) step. DNA was quantified, tested using Real-time PCR for 16S rDNA and S. aureus and, then, microbiome was evaluated. RESULTS: Although 16S rDNA was similarly detected across all the different techniques, Roche kit gave the highest DNA yield. The lowest Ct values for Real-time PCR for S. aureus was identified when lysostaphin was added. Considering genera from microbiome, alpha diversity indices did not show any significant differences between techniques, while relative abundances were more similar in presence of DTT. CONCLUSIONS: None of the conditions emerged to be superior to the others even if enzyme-based kits seem to be needed in order to have a higher extraction yield.

18.
Respir Med ; 145: 120-129, 2018 12.
Article in English | MEDLINE | ID: mdl-30509700

ABSTRACT

BACKGROUND: International guidelines recommend simple spirometry for bronchiectasis patients. However, pulmonary pathophysiology of bronchiectasis is very complex and still poorly understood. Our objective was to characterize lung function in bronchiectasis and identify specific functional sub-groups. METHODS: This was a multicenter, prospective, observational study enrolling consecutive adults with bronchiectasis during stable sate. Patients underwent body-plethysmography before and after acute bronchodilation testing, diffusing lung capacity (DLCO) with a 3-year follow up. Air trapping and hyperinflation were a residual volume (RV) > 120%predicted and a total lung capacity>120%predicted. Acute reversibility was: ΔFEV1 ≥12% and 200 mL from baseline (FEV1rev) and ΔRV ≥10% reduction from baseline (RVrev). Sensitivity analyses included different reversibility cutoffs and excluded patients with concomitant asthma or chronic obstructive pulmonary disease. RESULTS: 187 patients were enrolled (median age: 68 years; 29.4% males). Pathophysiological abnormalities often overlapped and were distributed as follows: air trapping (70.2%), impaired DLCO (55.7%), airflow obstruction (41.1%), hyperinflation (15.7%) and restriction (8.0%). 9.7% of patients had normal lung function. RVrev (17.6%) was more frequent than FEV1rev (4.3%). Similar proportions were found after multiple sensitivity analyses. Compared with non-reversible patients, patients with RVrev had more severe obstruction (mean(SD) FEV1%pred: 83.0% (24.4) vs 68.9% (26.2); P = 0.02) and air trapping (RV%pred, 151.9% (26.6) vs 166.2% (39.9); P = 0.028). CONCLUSIONS: Spirometry alone does not encompass the variety of pathophysiological characteristics in bronchiectasis. Air trapping and diffusion impairment, not airflow obstruction, represent the most common functional abnormalities. RVrev is related to worse lung function and might be considered in bronchiectasis' workup and for patients' functional stratification.


Subject(s)
Bronchiectasis/diagnosis , Bronchiectasis/physiopathology , Residual Volume , Aged , Female , Follow-Up Studies , Humans , Lung Volume Measurements , Male , Middle Aged , Prospective Studies , Pulmonary Ventilation , Respiratory Function Tests , Severity of Illness Index , Spirometry , Time Factors
19.
Int J Mol Sci ; 19(10)2018 Oct 20.
Article in English | MEDLINE | ID: mdl-30347804

ABSTRACT

Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for S. aureus. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased S. aureus detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples.


Subject(s)
DNA, Bacterial/chemistry , Microbiota , Molecular Diagnostic Techniques/methods , Sequence Analysis, DNA/methods , Sputum/microbiology , Adult , DNA, Bacterial/genetics , Humans , RNA, Ribosomal, 16S/genetics
20.
Multidiscip Respir Med ; 13(Suppl 1): 29, 2018.
Article in English | MEDLINE | ID: mdl-30151190

ABSTRACT

BACKGROUND: Bronchiectasis is the final result of different processes and most of the guidelines advocate for a careful evaluation of those etiologies which might be treated or might change patients' management, including cystic fibrosis (CF). MAIN BODY: CFTR mutations have been reported with higher frequency in bronchiectasis population. Although ruling out CF is considered as a main step for etiological screening in bronchiectasis, CF testing lacks of a standardized approach both from a research and clinical point of view. In this review a list of most widely used tests in CF is provided. CONCLUSIONS: Exclusion of CF is imperative for patients with bronchiectasis and CFTR testing should be implemented in usual screening for investigating bronchiectasis etiology. Physicians taking care of bronchiectasis patients should be aware of CFTR testing and its limitations in the adult population. Further studies on CFTR expression in human lung and translational research might elucidate the possible role of CFTR in the pathogenesis of bronchiectasis.

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