Current Respiratory Medicine Reviews - Volume 15, Issue 2, 2019

Chronic obstructive pulmonary disease (COPD) is a common and progressive disorder which is characterised by pathological abnormalities driven by chronic airway inflammation. The assessment of airway inflammation in routine clinical practice in COPD is limited to surrogate blood markers. Fractional exhaled nitric oxide (FENO) is a marker of eosinophilic airway inflammation in asthma, and it can predict steroid responsiveness and help tailor corticosteroid treatment. The clinical value of FENO in COPD is less evident, but some studies suggest that it may be a marker of the eosinophilic endotype. More importantly, mathematical methods allow investigation of the alveolar/small airway production of NO which potentially better reflects inflammatory changes in anatomical sites, most affected by COPD. This review summarises the pathophysiological role of nitric oxide in COPD, explains the methodology of its measurement in exhaled air and discusses clinical findings of FENO in COPD.

Chronic obstructive lung disease is a common and preventable disease. One of its pathophysiological consequences is the presence of carbon dioxide retention due to hypoventilation and ventilation/perfusion mismatch, which in consequence will cause a decrease in the acid/base status of the patient. Whenever a patient develops an acute exacerbation, acute respiratory hypercapnic failure will appear and the necessity of a hospital ward is a must. However, current guidelines exist to better identify these patients and make an accurate diagnosis by using clinical skills and laboratory data such as arterial blood gases. Once the patient is identified, rapid treatment will help to diminish the hospital length and the avoidance of intensive care unit. On the other hand, if there is the existence of comorbidities such as cardiac failure, gastroesophageal reflux disease, pulmonary embolism or depression, it is likely that the patient will be admitted to the intensive care unit with the requirement of intubation and mechanical ventilation.

Despite being a disease with the constantly rising social burden and mortality, COPD is also associated with a number of other conditions known as comorbidities. COPD and other diseases often share similar risk factors, such as smoking and aging, which leads to increased prevalence of comorbidities. The key pathogenic mechanisms of COPD are chronic inflammation and oxidative stress and they also contribute significantly to the development of accompanying diseases. Through complex interactions, COPD increases the risk for certain comorbidities and they, in turn, have a negative impact on health status and contribute to mortality in COPD patients. Proper treatment of comorbidities may have a beneficial effect on COPD natural course and progression. Here we review the prevalence of the most common comorbidities of COPD; their interrelating mechanism and the current advances of the treatment in terms of co-existence.

Triple inhaled therapy for Chronic Obstructive Pulmonary Disease (COPD) includes an inhaled corticosteroid (ICS), a long-acting b2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) taken in combination. Triple therapy is recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) for patients who experience recurrent exacerbations despite treatment with either a dual bronchodilator or LABA/ICS combination. There is consistent evidence that the LABA/LAMA/ICS combination has significantly greater effects on trough FEV1, symptoms, quality of life, and exercise performance compared to comparator treatments. The role of triple therapy in reducing exacerbations in COPD patients is debatable, but recent trials have revealed some intriguing insights. Three pivotal studies, namely TRILOGY, TRINITY and TRIBUTE have been conducted to evaluate the safety and efficacy of extrafine Beclomethasone/Formoterol Fumarate/Glycopyrronium Bromide (BDP/FF/GB) versus different treatment options for COPD. Extrafine BDP/FF/GB has been compared to an ICS/LABA (BDP/FF) combination in the TRILOGY study, to a LAMA monotherapy (Tiotropium-TIO) and an extemporary triple combination of ICS/LABA + LAMA (BDP/FF + TIO) in the TRINITY study, and to one inhalation of LABA/LAMA per day (Indacaterol/ Glycopyrronium - IND/GLY) in the TRIBUTE study. Another triple therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) was recently tested in two further studies that included patients with COPD. The FULFIL study compared the efficacy of the triple FF/UMEC/VI therapy to the ICS/LABA association budesonide/formoterol, while the IMPACT study compared the rate of moderate and severe exacerbations between singleinhaler FF/UMEC/VI and single-inhaler FF/VI or UMEC/VI.

COPD and Type 2 diabetes are two highly prevalent global health conditions associated with high mortality and morbidity. The connection between these two common diseases is complex, and more research is required for further understanding of these conditions. COPD is being increasingly recognized as a risk factor for the development of type2 diabetes through different mechanisms including systemic inflammation, obesity, hypoxia and use of corticosteroids. Also, hyperglycemia in diabetes patients is linked to the adverse impact on lung physiology, and a possible increase in the risk of COPD. In this review article, we discuss the studies demonstrating the associations between COPD and Type 2 Diabetes, underlying pathophysiology and recommended therapeutic approach in the management of patients with coexisting COPD and diabetes.

The benefit of non-invasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) remains controversial. However, there is increasingly more evidence of NIV efficiency, especially high-flow NIV. This review presents the old and the new evidence of NIV effectiveness in stable COPD, considering pathophysiological arguments for NIV in COPD. Guidelines, randomized controlled trials (RCTs) and crossover studies included in review and metaanalysis based on patient-reported outcomes (PROs) have been analyzed. The role of NIV in rehabilitation and in palliative care and the role of telemedicine in relation with NIV are still up for debate. Challenges in choosing the right device and the optimal mode of ventilation still exist. There are also discussions on the criteria for patient inclusion and on how to meet them. More studies are needed to determine the ideal candidate for chronic NIV and to explain all the benefits of using NIV.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, hyperinflation and reduced gas exchange that lead to progressive dyspnea. Pulmonary rehabilitation, lifestyle changes, pharmacotherapy, long-term oxygen therapy, noninvasive ventilation and surgical therapeutic approaches are the basic management strategies. Purpose: In the last 15 years, various bronchoscopic therapeutic modalities have emerged for severe COPD. The aim of this review is to summarize the effects of these bronchoscopic treatments compared with lung rehabilitation and pharmacological therapies. Methods: A PubMed search for the eligible studies and reviews on interventional bronchoscopy and COPD has been conducted. Results: Bronchoscopic lung volume reduction (LVR) techniques are targeted to reduce hyperinflation. The efficacy of reversible valve implantation has been confirmed in several randomized controlled trials. It provides clinical benefit in the absence of interlobar collateral ventilation. Nonblocking bronchoscopic LVR with coils, thermal vapor or sealants is independent of collateral ventilation but has not been studied sufficiently. Partially irreversible coil implantation leads to parenchymal compression while irreversible LVR with thermal vapor or sealants induce an inflammatory reaction. Targeted lung denervation ablates parasympathetic pulmonary nerves in COPD for sustainable bronchodilation, and liquid nitrogen metered cryospray destroys hyperplastic goblet cells and excessive submucous glands in the central airways to induce mucosal regeneration in chronic bronchitis. Conclusion: The best-examined bronchoscopic LVR method is the valve therapy. The data from the other modalities are still limited. Further studies are required to select the patients that will optimally benefit from a particular treatment and to predict and treat the procedure-related complications.

Health care systems worldwide are commonly burdened with COPD and lung cancer and subsequently much has been studied and learnt of the interdependence between these two clinical entities. Lung cancer surgical treatment options in patients with severe COPD remain a clinical challenge for the multidisciplinary team. Appropriate patient selection and prediction of postoperative pulmonary complications aid in surgical decision making and informed patient consent. In this review, we present an overview of surgical selection tools (lung function parameters, risk stratification for postoperative pulmonary complications) and lung cancer clinical outcomes (recurrence, survival) in patients with COPD undergoing lung cancer surgery.

Alpha-1 antitrypsin deficiency (AATD) or alpha-1 antitrypsin proteinase inhibitor (α1-Pi) deficiency, is a genetic disorder leading to a higher risk of pulmonary, hepatic and other organrelated diseases. The spectrum of diseases associated with AATD is large and includes pulmonary conditions (COPD, asthma, asthma-COPD overlap syndrome, bronchiectasis, etc.) as well as extrapulmonary (liver diseases, systemic vasculitis, rheumatoid arthritis, panniculitis, multiple sclerosis, peripheral neuropathy). We present a review of AATD focusing on its connection to other conditions.