Respiratory Function Changes as Early Signs of Amyotrophic Lateral Sclerosis.

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking. OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines. METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in 35 patients with unspecific neurological symptoms at the time of the visit and those were subsequently diagnosed with ALS 2 years after the initial visit ("pre-ALS"); we compared these patients with 29 patients with established ALS and with 28 control subjects. RESULTS: Spirometric parameters were not different between the three groups. However, MIP was significantly lower and P0.1 was significantly increased (with the ratio P0.1/MIP significantly higher) in both established and pre-ALS patients compared to controls, while both MIP and P0.1 were similar between established ALS and pre-ALS. CONCLUSIONS: Changes in MIP, P0.1, and P0.1/MIP ratio are highly suggestive of preclinical ALS when the spirometry and neurodiagnostic tests are still inconclusive. MIP and P0.1 are noninvasive measurements that can be easily assessed in an ambulatory setting. Future studies on larger cohorts are needed to validate the use of these parameters in the preclinical diagnosis of ALS as well as in other neuromuscular diseases.

Diagnosis of amyotrophic lateral sclerosis by respiratory function test.

The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, as the disease progresses, it is increasingly enriched by a rich set of symptoms and positive respiratory tests until respiratory failure occurs, which represents the main cause of death in ALS. Hereby we analyze the main pulmonary function tests (PFT) in the various stages of the disease, up to the recent evidence for the possibility of an early diagnosis.

Kidney and lung in pathology: mechanisms and clinical implications.

There is a close, physiological, relationship between kidney and lung that begin in the fetal age, and is aimed to keep homeostatic balance in the body. From a pathological point of view, the kidneys could be damaged by inflammatory mediators or by immune-mediated factors linked to a primary lung disease or, conversely, it could be the kidney disease that causes lung damage. Non-immunological mechanisms are frequently involved in renal and pulmonary diseases, as observed in chronic conditions. This crosstalk have clinical and therapeutic consequences. This review aims to describe the pulmonary-renal link in physiology and in pathological conditions.

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO).

Background: Italy has one of the world's oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertension medications may increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

RP EBUS as a guide for transbronchial pulmonary biopsy in the diagnosis of organizing pneumonia.

Diffuse parenchymal lung diseases (DPLDs) include a wide variety of manifestations characterized by different degrees of inflammation and fibrosis with various patterns of secondary lobule alterations, such that the diagnosis often requires histopathological confirmation in addition to clinical and radiological data. Radial probe endobronchial ultrasonography (RP EBUS) can be used as a guide for transbronchial pulmonary biopsy (TBPB) to obtain tissue samples, and thus can be a useful tool in the diagnostic management of peripheral pulmonary lesions. Organizing pneumonia (OP) is a particular type of DPLD characterized by lung inflammation and scarring that obstruct the small airways and air sacs of the lung. In this study, we describe how and when RP EBUS can be used to guide TBPB and significantly help in the diagnosis of OP.

Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: a proof-of-concept study.

Domiciliary non-invasive ventilation (NIV) effectively reduces arterial carbon dioxide pressure (PaCO2) in patients with stable hypercapnic chronic obstructive pulmonary disease, but a consistent percentage of them may remain hypercapnic. We hypothesised that extracorporeal CO2 removal (ECCO2R) may lower their PaCO2 Ten patients hypercapnic despite ≥6 months of NIV underwent a 24-hour trial of ECCO2R. Six patients completed the ECCO2R-trial with a PaCO2 drop ranging between 23% and 47%. Time to return to baseline after interruption ranged 48-96 hours. In four patients, mechanical events led to ECCO2R premature interruption, despite a decreased in PaCO2 This time window 'free' from hypercapnia might allow to propose the concept of 'CO2 dialysis'.

SARS-CoV-2 pandemic in Italy: ethical and organizational considerations.

The current SARS-CoV-2 pandemic is still raging in Italy. The country is currently plagued by a huge burden of virusrelated cases and deaths. So far, the disease has highlighted a number of problems, some in common with other Countries and others peculiar to Italy which has suffered from a mortality rate higher than that observed in China and in most Countries in the world. The causes must be sought not only in the average age of the population (one of the oldest in the world), but also in the inconsistencies of the regional health systems (into which the National Health System is divided) and their delayed response, at least in some areas. Ethical issues emerged from the beginning, ranging from restrictions on freedom of movements and restrictions on personal privacy due to the lockdown, further to the dilemma for healthcare professionals to select people for ICU hospitalization in a shortage of beds in Intensive Care Unit (ICU). Organizational problems also emerged, although an official 2007 document from the Ministry of Health had planned not only what measures had to be taken during an epidemic caused by respiratory viruses, but also what had to be done in the inter-epidemic period (including the establishment of DPIs stocks and ventilators), vast areas of Italy were totally unprepared to cope with the disease, as a line of that document was not implemented. Since organizational problems can worsen (and even cause) ethical dilemmas, every effort should be made in the near future to prepare the health system to respond to a similar emergency in a joint, coherent, and homogeneous way across the Country, as planned in the 2007 document. In this perspective, Pulmonary Units and specialists can play a fundamental role in coping with the disease not only in hospitals, as intermediate care units, but also at a territorial level in an integrated network with GPs.

COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature.

BACKGROUND: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID- 19). METHODS: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. A total of 205 articles were identified and 53 were included in this review. RESULTS: We describe the ongoing COVID-19 therapies that should be known by oncologists and highlight the potential interactions with antineoplastic drugs, commonly used in clinical practice. The main drug interactions were found with tocilizumab, ruxolitinib and colchicine. CONCLUSIONS: The literature provides an inconclusive picture on potential preferred treatments for COVID-19 and their interactions with antineoplastic agents. Future clinical trials are needed to better understand the interactions between different drugs in the context of COVID-19 pandemic.

Montelukast Improves Symptoms and Lung Function in Asthmatic Women Compared With Men.

Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse responses to drugs. However, there are knowledge gaps on the effectiveness of anti-leukotrienes drugs on lung function, symptoms, and pulmonary and systemic inflammation in adult asthmatic women compared with men. We conducted a prospective cohort study to characterize the effectiveness of an anti-leukotrienes drug, montelukast (MS), in asthmatic adult women and men. Methods: Twenty-one asthmatic subjects (11 women and 10 men), who were on low-dose inhaled corticosteroids (ICS), were treated with MS. The optimal control of the symptoms was achieved in both groups according to the Global Initiative for Asthma guidelines. At enrollment, and after 13 weeks from the beginning of MS, pulmonary function tests and asthma control tests were performed, and the fraction of exhaled nitric oxide and blood eosinophils levels were measured. Results: From baseline until the end of the study, women treated with MS + ICS had better control of the asthmatic symptoms, defined as higher asthma control test (ACT) score (17.00 ± 1.07 to 23.36 ± 0.45; p < 0.0015), improved pulmonary function [with higher forced expiratory volume in 1 s (from 77.25 ±â€¯6.79 to 103.88 ± 6.24; p < 0.0077)], and forced vital capacity (from 91.95 ± 6.81 to 113.17 ± 4.79; p < 0.0183) compared with men. Interestingly, MS + ICS-treated women had significantly lower levels of blood eosinophils (from 5.27 ±â€¯0.30 to 3.30 ±â€¯0.31; p < 0.0449) and exhaled nitric oxide (from 44.70 ± 7.30 to 25.20 ± 3.90; p < 0.0294) compared with men. Conclusion: The treatment with MS, added to ICS, in women leads to better control of symptoms, better management of lung function, and decreased inflammation levels compared with ICS + MS treatment in men.

Is early detection of late-onset Pompe disease a pneumologist's affair? A lesson from an Italian screening study.

BACKGROUND: Late-onset Pompe disease (LOPD) is a recessive disease caused by α-glucosidase (GAA) deficiency, leading to progressive muscle weakness and/or respiratory failure in children and adults. Respiratory derangement can be the first indication of LOPD, but the diagnosis may be difficult for pneumologists. We hypothesize that assessing the GAA activity in suspected patients by a dried blood spot (DBS) may help the diagnosis of LOPD in the pneumological setting. POPULATION AND METHODS: We performed a multicenter DBS survey of patients with suspected LOPD according to a predefined clinical algorithm. From February 2015 to December 2017, 140 patients (57 ± 16 yrs., 80 males) were recruited in 19 Italian pneumological units. The DBS test was performed by a drop of blood collected on absorbent paper. Patients with GAA activity < 2.6 µmol/L/h were considered positive. A second DBS test was performed in the patients positive to the first assay. Patients testing positive at the re-test underwent a skeletal muscle biopsy to determine the GAA enzymatic activity. RESULTS: 75 recruited subjects had outpatient access, 65 subjects were admitted for an acute respiratory failure episode. Two patients tested positive in both the first and second DBS test (1.4% prevalence), and the LOPD diagnosis was confirmed through histology, with patients demonstrating a deficient GAA muscle activity (3.6 and 9.1 pmol/min/mg). A further five subjects were positive in the first DBS test but were not confirmed at re-test. The two positive cases were both diagnosed after hospitalization for acute respiratory failure and need of noninvasive ventilation. Most of the recruited patients had reduced maximal respiratory pressures (MIP 50 ± 27% and MEP 55 ± 27% predicted), restrictive pattern (FEV1/FVC 81.3 ± 13.6) and hypoxaemia (PaO2 70.9 ± 14.5 mmHg). Respiratory symptoms were present in all the patients, but only 48.6% of them showed muscle weakness in the pelvic girdle and/or in the scapular girdle (35.7%). CONCLUSIONS: DBS GAA activity test may be a powerful screening tool among pneumologists, particularly in the acute setting. A simple clinical algorithm may aid in the selection of patients on which to administer the DBS test.

Relationship Between Gender and the Effectiveness of Montelukast: An Italian/Danish Register-Based Retrospective Cohort Study.

Rationale: Gender-related differences in asthma prevalence, pathophysiology and clinical features induced by sex steroids have been investigated, however, how gender influences response to asthma treatments in routine clinical practice have not yet been elucidated fully. This aspect is crucial for montelukast considering the jeopardization of asthmatic patients that benefit from this treatment and the existence of evidence of gender differences in leukotriene levels. Therefore, to fulfill this medical need, we investigated the role of gender on a set of montelukast' effectiveness surrogates in adults and pediatric patients with asthma. Methods: The study settings were Napoli 2 Local Health Unit (southern Italy) and the entire Danish territory. The study population was composed of adult and pediatric patients with asthma. Cumulative incidence curves, unadjusted and adjusted Cox regression were used as statistical models to compare aforementioned outcomes between genders. Results: Adult Italian male users of montelukast had a statistically lower persistence in montelukast treatment compared to female users. In the adjusted analyses, they had a higher hazard of montelukast' withdrawal (Hazard Ratio [HR] 1.07; 95% Confidence Interval [CI] 1.01-1.14), add-on/switch to a long-term treatment for asthma following montelukast withdrawal (HR 1.72; 95%CI 1.39-2.12), and rescue therapy with short-acting ß2 agonist (HR 1.24; 95%CI 1.04-1.47). In the adult Danish cohort, we also found that male users had higher a hazard of rescue therapy with oral corticosteroids (HR 1.10; 95%CI 1.04-1.16). In the pediatric cohorts, no statistically significant differences were observed between genders for aforementioned outcomes. Conclusions: In adults, male gender was associated with increased hazards of montelukast discontinuation, add-on/switch to a long-term treatment for asthma following montelukast withdrawal, and rescue therapy with oral corticosteroids or short-acting ß2 agonist when compared to the female gender. As expected, these associations were reversed or absent in pediatric patients.

COPD management as a model for all chronic respiratory conditions: report of the 4th Consensus Conference in Respiratory Medicine.

BACKGROUND: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. METHODS: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. RESULTS AND CONCLUSIONS: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.

In the era of ultrasound technology, could conventional trans-bronchial needle aspiration still play a role in lung cancer mediastinal staging?

BACKGROUND: To evaluate the feasibility of a combined strategy including conventional-trans-bronchial needle aspiration biopsy (C-TBNA) and endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) for sampling mediastinal adenopathies in patients with lung cancer in order to determinate whether in the era of ultrasound technology C-TBNA could still play a role in mediastinal staging. METHODS: It was a retrospective multicenter study including all consecutive patients with lung cancer and radiological mediastinal adenopathies undergoing TBNA for mediastinal staging (January 2014 - July 2016). C-TBNA was performed as first diagnostic procedure. All negative C-TBNA results were corroborated by EBUS-TBNA, and, if EBUS-TBNA was negative, by mediastinoscopy or surgery. The diagnostic yield of C-TBNA were then calculated. RESULTS: A total of 175 patients were included in the study for a total of 197 mediastinal adenopathies sampled. C-TBNA was positive in 125 cases and negative in 72 cases who underwent EBUS-TBNA. It was positive in 58 cases and negative in 14 patients. After surgical exploration (n=12) and mediastinoscopy (n=2), 11 patients did not present metastases (true negative) while 3 presented mediastinal involvement (false negative). Thus, C-TBNA had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 67.2%, 100%, 100%, 15.3% and 69.0%, respectively. The sensitivity increased for sampling paratracheal versus subcarinal stations (80% versus 49%; P<0.001); and large adenopathies (≥15 mm) versus small adenopathies (<15 mm) (83% versus 43%; P<0.001). In all re-staging patients (n=4), Conventional-TBNA results were false negative. CONCLUSIONS: The combined use of C-TBNA and EBUS-TBNA as the most cost-effective strategy in the setting of mediastinal staging. C-TBNA performed before EBUS-TBNA is indicated for sampling large mediastinal adenopathies near to carina while EBUS-TBNA remains the first choice for puncturing small adenopathies far from carina and for re-staging after induction therapy.

Three-dimensional virtual bronchoscopy using a tablet computer to guide real-time transbronchial needle aspiration.

Objectives: We proposed a new virtual bronchoscopy tool to improve the accuracy of traditional transbronchial needle aspiration for mediastinal staging. Methods: Chest-computed tomographic images (1 mm thickness) were reconstructed with Osirix software to produce a virtual bronchoscopic simulation. The target adenopathy was identified by measuring its distance from the carina on multiplanar reconstruction images. The static images were uploaded in iMovie Software, which produced a virtual bronchoscopic movie from the images; the movie was then transferred to a tablet computer to provide real-time guidance during a biopsy. To test the validity of our tool, we divided all consecutive patients undergoing transbronchial needle aspiration retrospectively in two groups based on whether the biopsy was guided by virtual bronchoscopy (virtual bronchoscopy group) or not (traditional group). The intergroup diagnostic yields were statistically compared. Results: Our analysis included 53 patients in the traditional and 53 in the virtual bronchoscopy group. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the traditional group were 66.6%, 100%, 100%, 10.53% and 67.92%, respectively, and for the virtual bronchoscopy group were 84.31%, 100%, 100%, 20% and 84.91%, respectively. The sensitivity ( P = 0.011) and diagnostic accuracy ( P = 0.011) of sampling the paratracheal station were better for the virtual bronchoscopy group than for the traditional group; no significant differences were found for the subcarinal lymph node. Conclusions: Our tool is simple, economic and available in all centres. It guided in real time the needle insertion, thereby improving the accuracy of traditional transbronchial needle aspiration, especially when target lesions are located in a difficult site like the paratracheal station.

Bronchoscopic lung volume reduction with endobronchial valves for heterogeneous emphysema: long-term results.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with implant of one-way endobronchial valves (EBV) is a feasible treatment for management of heterogeneous emphysema (HE) with clinical benefits in the early follow-up. We aimed to evaluate the long-terms results and safety of this procedure in a consecutive series of patients with HE. METHODS: It was a retrospective single center study including all consecutive patients with HE undergoing EBV treatment and completing at least 5 years of long-term follow-up. Patients were splitted into Collapse and No-Collapse Group if a lobar collapse or not were obtained after valves implant. The difference of functional data and quality of life (QoL) before and after the procedure (measured at 3, 6, 9, 12 months from the valve implantation, and then annually up to a maximum of 5 years) were statistically evaluated to show the long-term benefits of the procedure (primary endpoint). Yet, morbidity, mortality and survival rates were also recorded to show the safe of the treatment (secondary endpoint). RESULTS: Thirty-three patients were included in the study. Of these, three patients underwent a bilateral treatment. Collapse Group patients (n=27) presented a significant improvement in FEV1% (+17%; P=0.001); in FVC% (+18%; P=0.002); in RV% (-39%; P=0.003); in 6MWT (P=0.001) and in SGRQ (P=0.001) in the early 12 months of follow-up and no significant decline was seen later. Conversely, No-Collapse Group (n=9) did not have significant benefits. No major complications and death related to the procedure were observed. The 1-,2-,3-,4- and 5-year survival rates were 100%, 90%, 78%, 71% and 71%, respectively. Collapse Group had a better survival than No-Collapse Group (45 vs. 24 months; P=0.001). CONCLUSIONS: Our study confirmed that the lobar collapse is the key success of EBV treatment and the early improvements of respiratory function could be maintained up to five years from the valves implant.

Acid-base balance, serum electrolytes and need for non-invasive ventilation in patients with hypercapnic acute exacerbation of chronic obstructive pulmonary disease admitted to an internal medicine ward.

BACKGROUND: Hypoventilation produces or worsens respiratory acidosis in patients with hypercapnia due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In these patients acid-base and hydroelectrolite balance are closely related. Aim of the present study was to evaluate acid-base and hydroelectrolite alterations in these subjects and the effect of non-invasive ventilation and pharmacological treatment. METHODS: We retrospectively analysed 110 patients consecutively admitted to the Internal Medicine ward of Cava de' Tirreni Hospital for acute exacerbation of hypercapnic chronic obstructive pulmonary disease. On admission all patients received oxygen with a Venturi mask to maintain arterial oxygen saturation at least >90 %, and received appropriate pharmacological treatment. Non-Invasive Ventilation (NIV) was started when, despite optimal therapy, patients had severe dyspnea, increased work of breathing and respiratory acidosis. Based on Arterial Blood Gas (ABG) data, we divided the 110 patients in 3 groups: A = 51 patients with compensated respiratory acidosis; B = 36 patients with respiratory acidosis + metabolic alkalosis; and C = 23 patients with respiratory acidosis + metabolic acidosis. 55 patients received only conventional therapy and 55 had conventional therapy plus NIV. RESULTS: The use of NIV support was lower in the patients belonging to group B than in those belonging to group A and C (25 %, vs 47 % and 96 % respectively; p < 0.01). A statistically significant association was found between pCO2 values and serum chloride concentrations both in the entire cohort and in the three separate groups. CONCLUSIONS: Our study shows that in hypercapnic respiratory acidosis due to AECOPD, differently from previous studies, the metabolic alkalosis is not a negative prognostic factor neither determines greater NIV support need, whereas the metabolic acidosis in addition to respiratory acidosis is an unfavourable element, since it determines an increased need of NIV and invasive mechanical ventilation support.

Sequential Bilateral Bronchoscopic Lung Volume Reduction With One-Way Valves for Heterogeneous Emphysema.

BACKGROUND: Clinical benefits of bronchoscopic lung volume reduction with one-way endobronchial valves have been reported for heterogeneous emphysema after unilateral treatment. We assessed the potential role of contralateral treatment to prolong the benefits obtained with the first procedure. METHODS: This was a retrospective multicenter study including consecutive patients with heterogeneous emphysema undergoing bronchoscopic valves deployment during the last 4 years. Patients were split into two groups depending on the procedure (unilateral versus bilateral). The intergroup differences were evaluated to assess the viability, effectiveness, and safety of the bilateral procedure. RESULTS: Forty-nine patients were enrolled. Of these, 14 (28%) had a sequential bilateral procedure mainly due to loss of the clinical benefits obtained with the first treatment. A significant improvement of forced expiratory volume in 1 second (p < 0.05), forced vital capacity (p < 0.05), residual volume (p < 0.05), 6-minute walking test (p < 0.05), and St. George respiratory questionnaire (p < 0.02) was achieved after the second procedure. These results were maintained during follow-up. There was no significant difference regarding the changes of forced expiratory volume in 1 second (p = 0.4), forced vital capacity (p = 0.08), residual volume (p = 0.9), 6-minute walking test (p = 0.3), and St. George respiratory questionnaire (p = 0.1) between the bilateral and unilateral groups. CONCLUSIONS: A sequential bilateral approach seems to be a valid strategy to improve respiratory function in patients with bilateral heterogeneous emphysema who have lost the benefits obtained with the first procedure.