Lung Ultrasound Signs: The Beginning. Part 3-An Accademia di Ecografia Toracica Comprehensive Review on Ultrasonographic Signs and Real Needs.

Over the last 20 years, scientific literature and interest on chest/lung ultrasound (LUS) have exponentially increased. Interpreting mixed-anatomical and artifactual-pictures determined the need of a proposal of a new nomenclature of artifacts and signs to simplify learning, spread, and implementation of this technique. The aim of this review is to collect and analyze different signs and artifacts reported in the history of chest ultrasound regarding normal lung, pleural pathologies, and lung consolidations. By reviewing the possible physical and anatomical interpretation of these artifacts and signs reported in the literature, this work aims to present the AdET (Accademia di Ecografia Toracica) proposal of nomenclature and to bring order between published studies.

Assessing the relationship between cardiovascular and small airway disease and acute events in COPD: The ARCADIA study protocol.

The initial alterations of chronic obstructive pulmonary disease (COPD) involve the small airways. Small airway disease (SAD) is related to lung hyperinflation and air trapping. Several lung function tests may detect the presence of SAD, namely forced mid-expiratory flows, residual volume (RV), RV/total lung capacity (TLC) ratio, functional residual capacity, airway resistances obtained with body-plethysmography and oscillometry, and the single-breath nitrogen washout test. Additionally, high-resolution computed tomography can detect SAD. In addition to SAD, COPD is related to cardiovascular disease (CVD) such as heart failure, peripheral vascular disease, and ischemic heart disease. No studies have assessed the relationship between CVD, COPD, and SAD. Therefore, the main objective of the Assessing the Relationship between Cardiovascular and small Airway Disease and Acute events in COPD (ARCADIA) study is to assess the risk of CVD in COPD patients according to SAD in a real-life setting. The correlation between CVD, mortality, and acute exacerbation of COPD (AECOPD) is also evaluated. ARCADIA is a 52-week prospective, multicentre, pilot, observational, cohort study conducted in ≥22 pulmonary centres in Italy and that enrols ≥500 COPD patients, regardless of disease severity (protocol registration: ISRCTN49392136). SAD is evaluated at baseline, after that CVD, mortality, and AECOPD are recorded at 6 and 12 months. Bayesian inference is used to quantify the risk and correlation of the investigated outcomes in COPD patients according to SAD. The ARCADIA study provides relevant findings in the daily clinical management of COPD patients.

Low arousal threshold: a common pathophysiological trait in patients with obstructive sleep apnea syndrome and asthma.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma. METHODS: A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%. RESULTS: Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference (p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant. CONCLUSIONS: This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor.

Future Perspectives of Revaluating Mild COPD.

In 2020, COPD was the third leading cause of death worldwide. Lung function is central for the diagnosis of this disease, and COPD severity is still partially classified based on airflow obstruction, which can range from "mild" (GOLD 1 group, FEV1 ≥80% predicted) to "very severe" (GOLD 4, FEV1 <30% predicted). However, the term "mild COPD" needs to be carefully analyzed. Several studies have shown that even in the presence of a mild obstruction, patients can have significant symptoms, physiological deterioration, evidence of emphysema, and suffer from recurrent exacerbations. Small airways pathology significantly correlates with the presence of symptoms, and it has been demonstrated that the onset of bronchiolitis occurs earlier than that of emphysema. These damages have long been known to not be detectable with conventional tests, and exclusive reliance on spirometry is not enough to adequately study and stage a patient with "mild COPD." Therefore, early identification of COPD is of utmost importance in the light of modifying the natural course of the disease. However, patients with early lung damage are yet to be included and studied in interventional clinical trials.

Dysphagia symptoms in obstructive sleep apnea: prevalence and clinical correlates.

BACKGROUND: Epidemiology of dysphagia and its drivers in obstructive sleep apnea (OSA) are poorly understood. The study aims to investigate the prevalence of dysphagia symptoms and their association with demographic and clinical factors in patients with OSA. METHODS: Patients with OSA referring to an Academic Sleep Outpatient Clinic were enrolled in a prospective study. Demographic, clinical characteristics, and OSA symptoms were collected. All patients underwent home sleep cardiorespiratory polygraphy and the Eating-Assessment Tool questionnaire (EAT-10) to investigate dysphagia symptoms. Patients with a positive EAT-10 were offered to undergo a fiberoptic endoscopic evaluation of swallowing (FEES) to confirm the presence of dysphagia. FEES findings were compared with a healthy control group. Univariate and multivariate analyses were performed to assess predictors of dysphagia. RESULTS: 951 patients with OSA (70% males, age 62 IQR51-71) completed the EAT-10, and 141 (15%) reported symptoms of dysphagia. Female gender (OR = 2.31), excessive daily sleepiness (OR = 2.24), number of OSA symptoms (OR = 1.25), anxiety/depression (OR = 1.89), and symptoms of gastroesophageal reflux (OR = 2.75) were significantly (p < 0.05) associated with dysphagia symptoms. Dysphagia was confirmed in 34 out of 35 symptomatic patients that accepted to undergo FEES. Patients with OSA exhibited lower bolus location at swallow onset, greater pharyngeal residue, and higher frequency and severity of penetration and aspiration events than healthy subjects (p < 0.05). CONCLUSION: A consistent number of patients with OSA show symptoms of dysphagia, which are increased in females and patients with a greater OSA symptomatology, anxiety and depression, and gastroesophageal reflux. The EAT-10 appears a useful tool to guide the selection of patients at high risk of dysphagia. In clinical practice, the integration of screening for dysphagia in patients with OSA appears advisable.

Switching to nebulised short acting bronchodilators does not increase the risk of arrhythmia in patients hospitalized with a COPD exacerbation.

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.

Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study.

Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 µg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 µg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.

Correction to: Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective.

An amendment to this paper has been published and can be accessed via the original article.

Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients.

BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.

Current and future targeted therapies for severe asthma: Managing treatment with biologics based on phenotypes and biomarkers.

Asthma is a respiratory disorder with considerable heterogeneity in aetiology, triggers, clinical characteristics and response to therapy. This diversity reflects different inflammatory pathways that can be subdivided into clinically similar categories called phenotypes, or pathogenically comparable groups called endotypes. In recent years, a great amount of research has been dedicated to the investigation and understanding of the heterogeneity of asthma pathophysiology and to the identification of treatable traits, biomarkers, mediators and therapeutic targets. Severe asthma is defined as an uncontrolled disease despite a maximal conventional therapeutic approach. While, to date, some target therapies showing improvements in lung function, asthma symptoms and a reduction of the annual rate of exacerbations in patients with severe asthma have been already approved, other treatments are currently being studied, specifically targeting Type 2 asthma. Further progress however, is still needed to tackle the molecular pathways for non-Type 2 asthma. The aim of the present narrative review is to discuss and examine the indication, mechanisms of action and therapeutic effects of currently available and emerging biologic agents for the treatment of severe asthma.

Rationale underlying the measurement of fractional exhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease characterised by tissue fibrosis leading to vascular injury. Nitric oxide (NO) has been implicated in the pathogenesis of autoimmune diseases. A deficiency in basal NO production by the constitutive endothelial isoform of nitric oxide synthase may promote vasoconstriction and vascular wall thickening. In January 2017, we searched the PubMed/Medline, Cochrane Library and Enbase/Medline databases for studies analysing physio-pathological correlations with lung fractional exhaled NO (FeNO) production. This review describes the rationale underlying possible applications of FeNO measurements in the management of SSc. Measuring NO levels at multiple expiratory flow rates makes it possible to distinguish airway NO production and distal airway/alveolar NO concentration (ANOC), and there is increasing evidence indicating that it may be useful in many non-respiratory conditions. FeNO levels are increased in SSc patients with fibrosing lung disease, whereas those with pulmonary hypertension have relatively low FeNO levels, thus suggesting that NO plays an important role in regulating pulmonary vascular resistance in SSc. However, a number of studies have shown increased ANOC in SSc patients without increased FeNO levels. The relationship between lung diffusing capacity for carbon monoxide and ANOC may be related to increased alveolar membrane thickness impeding NO diffusion or alveolar inflammation in SSc lung disease. The findings concerning the usefulness of FeNO measurements in SSc patients are discordant, but the available papers suggest that ANOC is a more accurate indicator of progressive lung dysfunction and an increase in ANOC could assess the extent of interstitial lung disease non-invasively.

Clinical and Functional Characteristics of COPD Patients Across GOLD Classifications: Results of a Multicenter Observational Study.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. The severity grading systems proposed by the Global initiative for Chronic Obstructive Lung Disease (GOLD) have changed over time. The aim of the study was to evaluate if the different GOLD classifications can capture the complexity of the disease by investigating the distribution of lung function and clinical parameters across the GOLD classification systems. This was an observational, retrospective, multicentre study. COPD patients were stratified according to the GOLD severity grading proposed in the 2007, and to the ABCD assessment tool present in the 2011, and 2017 versions of the initiative. Data from body plethysmography, DLCO, comorbidities, exacerbation history, pharmacological therapy and eosinophil counts were collected. A total of 1360 patients (73.4% males) were included in the analysis. Overall, 37% of the patients were severe-very severe according to GOLD 2007. Compared with GOLD 2011, applying the GOLD 2017 criteria, the proportion of the at risk categories (C and D) was reduced by ∼23%. Impairment in inspiratory capacity, DLCO and the prevalence of emphysema paralleled the GOLD 2007 classification only. The proportion of patients with ≥ 200 eosinophils/µL was higher in GOLD 2007 stages 3-4 compared with stages 1-2 (P = 0.008). Eosinophil levels were similar across risk classes in GOLD 2011 and 2017. Overall, 41.8% and 52.4% of the patients in the low risk groups according to GOLD 2011 and 2017 were exposed to inhaled corticosteroids. The GOLD 2011 and 2017 classifications, despite exploring symptoms and exacerbations, might miss other relevant patients' clinical characteristics such as lung function and phenotypes, which have a significant impact on outcomes and disease severity.

Effects of bronchodilation on biomarkers of peripheral airway inflammation in COPD.

Peripheral airway inflammation and dysfunction are key elements in the pathogenesis of COPD. The exhaled alveolar fraction of nitric oxide (CANO) is an indirect biomarker of lung peripheral inflammation. We tested whether inhaled long-acting bronchodilators (LABA) can affect CANO and we evaluated correlations with lung mechanics in patients with COPD. Two-centre, randomised, double blind, crossover study including COPD patients with moderate-to-severe airflow obstruction. Following a pharmacological washout, multi-flow exhaled fraction of NO (FENO), plethysmography, lung diffusion (DLCO), single breath nitrogen washout test and dyspnoea were measured in a crossover manner at baseline and 30, 60 and 180 min following administration of salmeterol (Sal) or formoterol fumarate (FF). (ClinicalTrials.gov, number NCT01853787). Fort-five patients were enrolled (median age: 71.8 years; 84.4% males). At baseline, CANO correlated with airway resistances (r = 0.422), residual volume/total lung capacity (RV/TLC; r = 0.375), transfer factor (r= -0.463) and forced expiratory volume in 1 s (FEV1; r= -0.375, all P < 0.01). After LABA administration, we found a significant reduction of FENO that reached statistical significance at 180'; no difference was found between FF and S. Consistently, a significant reduction of CANO was documented at 60' and 180' compared to baseline for both FF and S (P < 0.01 and P < 0.05, respectively). Changes in CANO were correlated with changes in vital capacity (r=-44; P < 0.001) and RV/TLC (r = 0.56; P < 0.001), but not FEV1. In COPD, direct correlations were found between the levels of CANO and the magnitude of peripheral airway dysfunction. LABA reduced CANO levels. The reduction was associated with improvement in functional parameters reflecting air trapping.

Usefulness of six-minute walk test in systemic sclerosis.

The 6-minute walk test (6MWT) is a standardised, feasible and reliable measure of sub-maximal exercise capacity that has never been fully validated in systemic sclerosis (SSc). A variety of data suggest that many non-pulmonary aspects of SSc contribute to the test results, thus blunting the ability of the 6MWT to measure changes in lung function. Sources of variability are a training effect, technician experience, subject encouragement, medication, other activities on day of testing, deconditioning and the effects of musculoskeletal conditions and pain. Another cause of variability is the anatomical site the probe is attached to: a forehead probe is preferable to a finger or earlobe sensor. The indiscriminate use of the 6MWT for all SSc patients is not useful. It should be used in patients with pulmonary involvement, combined with diffusion capacity of the lung for carbon monoxide (DLCO) and its components (membrane diffusion and capillary volume) or the Sclerodermia Health Assessment Questionnaire Disability Index. The use of these combined parameters may indicate the onset of pulmonary hypertension. Recent studies suggest two alternatives to the 6MWT: maximal cardiopulmonary exercise testing and DLCO testing during effort. However, their use must still be validated.

Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective.

BACKGROUND: Empirical antibiotic coverage for atypical pathogens in community-acquired pneumonia (CAP) has long been debated, mainly because of a lack of epidemiological data. We aimed to assess both testing for atypical pathogens and their prevalence in hospitalized patients with CAP worldwide, especially in relation with disease severity. METHODS: A secondary analysis of the GLIMP database, an international, multicentre, point-prevalence study of adult patients admitted for CAP in 222 hospitals across 6 continents in 2015, was performed. The study evaluated frequency of testing for atypical pathogens, including L. pneumophila, M. pneumoniae, C. pneumoniae, and their prevalence. Risk factors for testing and prevalence for atypical pathogens were assessed through univariate analysis. RESULTS: Among 3702 CAP patients 1250 (33.8%) underwent at least one test for atypical pathogens. Testing varies greatly among countries and its frequency was higher in Europe than elsewhere (46.0% vs. 12.7%, respectively, p < 0.0001). Detection of L. pneumophila urinary antigen was the most common test performed worldwide (32.0%). Patients with severe CAP were less likely to be tested for both atypical pathogens considered together (30.5% vs. 35.0%, p = 0.009) and specifically for legionellosis (28.3% vs. 33.5%, p = 0.003) than the rest of the population. Similarly, L. pneumophila testing was lower in ICU patients. At least one atypical pathogen was isolated in 62 patients (4.7%), including M. pneumoniae (26/251 patients, 10.3%), L. pneumophila (30/1186 patients, 2.5%), and C. pneumoniae (8/228 patients, 3.5%). Patients with CAP due to atypical pathogens were significantly younger, showed less cardiovascular, renal, and metabolic comorbidities in comparison to adult patients hospitalized due to non-atypical pathogen CAP. CONCLUSIONS: Testing for atypical pathogens in patients admitted for CAP in poorly standardized in real life and does not mirror atypical prevalence in different settings. Further evidence on the impact of atypical pathogens, expecially in the low-income countries, is needed to guidelines implementation.

Influence of autonomic nervous system dysfunction in the genesis of sleep disorders in fibromyalgia patients.

OBJECTIVES: Fibromyalgia (FM) is characterised by chronic musculoskeletal pain, autonomic nervous system (ANS) dysfunction, and disturbed sleep. The aim of this study was to evaluate the influence of ANS dysfunction on the genesis of sleep disorders. METHODS: Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep. RESULTS: The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest (p<0.05), and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient (p<0.01), and they had a higher proportion of stage 1 non-REM sleep (p<0.001), experienced many arousals and periodic limb movements (PLMs) per hour of sleep (p<0.001) and a high proportion of periodic breathing (PB%) (p<0.0001). Their cyclic alternating pattern (CAP) rate was significantly increased (p<0.001). During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR (p<0.001). The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep. CONCLUSIONS: Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity.

Avoiding misdiagnosis in patients with dyspnea and wheezing: a case report illustrating the clinical implications of fixation error.

BACKGROUND: Bronchial asthma is a heterogeneous respiratory condition which can be mimicked by a wide range of pathologies including upper airways stenosis. The accurate diagnosis of asthma, as with other conditions, may be influenced by fixation errors, which are common in medicine and occur when a physician concentrates on only one element of a clinical case without considering other relevant aspects. Here we report a challenging case characterized by the contemporaneous presence of a common disease, asthma, together with a rare respiratory disease, idiopathic tracheal stenosis. CASE PRESENTATION: The 56-year-old female patient, a former smoker, was referred to our outpatient clinic for exertional dyspnea and persistent wheezing. There were no other respiratory or systemic symptoms over the past three months, and a psychological component was suspected. Spirometry with flow-volume evaluation and bronchoscopy were the key elements to establish the diagnoses and provide treatments. Once the diagnosis of asthma was confirmed, the combination of the anti-inflammatory corticosteroid fluticasone and the rapid-acting bronchodilator formoterol in a single inhaler effectively controlled the patient's symptoms, confirming the favorable efficacy and safety profile which are reflected in the recommendations of the international guidelines. CONCLUSIONS: In this paper we describe the clinical investigations and interventions that eventually confirmed a diagnosis of asthma complicated by an idiopathic tracheal stenosis and led to effective treatment of the patient. Awareness of fixation error may avoid misdiagnosis in patients with respiratory disease and a complicated history at presentation.

Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity.

BACKGROUND: Lung diffusing capacity (DLCO) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify DLCO parameters is unknown. OBJECTIVES: To investigate changes in DLCO and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. METHODS: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, DLCO, transfer factor (KCO) and alveolar volume (VA), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a VA/TLC <0.8. RESULTS: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), DLCO (0.12 ± 0.63 mmol × min-1 kPa-1; p < 0.01), lung function and dyspnea. Comparable improvements in DLCO were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with VA/TLC <0.8 improved the DLCO increasing their VA (177 ± 69 ml; p < 0.01), patients with VA/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower DLCO at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild DLCO impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). CONCLUSIONS: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in DLCO, while ventilation inhomogeneity may limit improvements in exercise tolerance.