Preserved Ratio Impaired Spirometry (PRISm): A Global Epidemiological Overview, Radiographic Characteristics, Comorbid Associations, and Differentiation from Chronic Obstructive Pulmonary Disease.

Preserved Ratio Impaired Spirometry (PRISm) manifests notable epidemiological disparities across the globe, with its prevalence and influential factors showcasing pronounced diversities among various geographical territories and demographics. The prevalence of PRISm fluctuates considerably among regions such as Latin America, the United States, and Asian nations, potentially correlating with a myriad of determinants, including socioeconomic status, environmental factors, and lifestyle modalities. Concurrently, the link between PRISm and health risks and other disorders, especially its distinction and interrelation with chronic obstructive pulmonary disease (COPD), has become a pivotal subject of scientific enquiry. Radiographic anomalies, such as perturbations in the pulmonary parenchyma and structural alterations, are posited as salient characteristics of PRISm. Furthermore, PRISm unveils intricate associations with multiple comorbidities, inclusive of hypertension and type 2 diabetes, thereby amplifying the intricacy in comprehending and managing this condition. In this review, we aim to holistically elucidate the epidemiological peculiarities of PRISm, its potential aetiological contributors, its nexus with COPD, and its association with radiographic aberrations and other comorbidities. An integrative understanding of these dimensions will provide pivotal insights for the formulation of more precise and personalised preventative and therapeutic strategies.

Regional Gas Exchange Measured by 129 Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Hyperpolarized 129 Xe magnetic resonance imaging (MRI) provides a non-invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown. PURPOSE: To characterize changes in 129 Xe gas transfer function following administration of an inhaled long-acting beta-agonist/long-acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator. STUDY TYPE: Prospective. POPULATION: Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy. FIELD STRENGTH/SEQUENCES: Dedicated ventilation imaging used a multi-slice 2D gradient echo sequence. Three-dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1-point Dixon sequence. Imaging was acquired at 3 T. ASSESSMENT: 129 Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low ) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref ). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO ), were also performed before and after treatment. STATISTICAL TESTS: Paired t-test, Pearson correlation coefficient (r). RESULTS: Baseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post-treatment change in vendef + low (r = -0.49, P < 0.05 and r = -0.52, P < 0.05, respectively). CONCLUSION: LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129 Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations.

Introduction: There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting ß2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs. Materials and Methods: Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients' high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition. Results: HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were <1, indicating greater peripheral than central deposition (0.48±0.13, 0.48±0.13 and 0.49±0.13 for BDP, FF and GB, respectively; 1.96±0.84, 0.97±0.34 and 1.20±0.48 for FluF, VI and UMEC, respectively). Conclusions: Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.

Local expression profiles of vitamin D-related genes in airways of COPD patients.

Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.

Characteristics of COPD phenotypes classified according to the findings of HRCT and spirometric indices and its correlation to clinical characteristics.

INTRODUCTION: In recent years, there has been increasing interest in diagnosing various components of chronic obstructive pulmonary disease (COPD) using high-resolution computed tomography (HRCT). The present study was undertaken to evaluate HRCT features in patients with COPD. MATERIALS AND METHODS: Fifty patients of COPD (confirmed on Spirometry as per the GOLD guidelines 2014 guidelines) were enrolled, out of which 35 patients got a HRCT done. The Philips computer program for lung densitometry was used with these limits (-800/-1, 024 Hounsfield unit [HU]) to calculate densities, after validating densitometry values with phantoms. We established the area with a free hand drawing of the region of interest, then we established limits (in HUs) and the computer program calculated the attenuation as mean lung density (MLD) of the lower and upper lobes. RESULTS: There was a significant correlation between smoking index and anteroposterior tracheal diameter (P = 0.036). Tracheal index was found to be decreasing with increasing disease severity which was statistically significant (P = 0.037). A mild linear correlation of pre-forced expiratory volume in the first second (FEV1) was observed with lower lobe and total average MLD while a mild linear correlation of post-FEV1 was observed with both coronal (P = 0.042) and sagittal (P = 0.001) lower lobes MLD. In addition, there was a linear correlation between both pre (P = 0.050) and post (P = 0.024) FEV1/forced vital capacity with sagittal lower lobe MLD. CONCLUSION: HRCT may be an important additional tool in the holistic evaluation of COPD.

Evaluation of bronchoscopic lung volume reduction coil treatment results in patients with severe emphysema.

INTRODUCTION: Bronchoscopic lung volume reduction coil (BLVR-C) implantation is an alternative therapeutic approach that can be applied together with medical treatment for patients with severe emphysema. BLVR-C is both easier and safer in terms of complications than volume reduction surgery. This study aimed to evaluate medium-term outcomes following BLVR-C treatment. METHODS: Forty patients who underwent BLVR-C between September 2013 and March 2014 were reviewed retrospectively. We compared changes between the baseline and 6-month post-procedural results with respect to pulmonary function tests, a 6-min walk test (6MWT), chronic obstructive pulmonary disease (COPD) assessment test (CAT), St. George's Respiratory Questionnaire (SGRQ), and pulmonary artery pressure (PAP) and arterial blood gas analyses. Secondary outcomes included procedure-related and follow-up complications. RESULTS: An average of 9.5 (range: 5-11) coils were placed per lung in an average procedural duration of 20.8 ± 7.0 min (range: 9-45) min. Six months after BLVR-C treatment, significant improvements were observed in patients' pulmonary function tests and quality of life. Changes were observed in the forced exhalation volume in 1 s (+150 mL), residual volume (-14.5%), 6MWT (+48 m), SGRQ (-10.5) and CAT Score (-7.5). Changes in the PAP and partial pressure of carbon dioxide values were not significant, and pneumothorax did not occur. In a 6-month follow-up, 11 cases of COPD exacerbation (41.4%), 7 cases of pneumonia (16.9%) and 1 death (2%) occurred. Treatment in 1 case was postponed because of hypotension and bradycardia during the process. CONCLUSION: BLVR-C treatment appears to be effective over the medium-term and safe for patients with severe emphysema.

Effects of aclidinium on determinants of COPD severity: symptoms and quality of life.

The pathophysiology of chronic obstructive pulmonary disease (COPD) includes persistent airflow limitation, altered gas exchange, and enhanced chronic inflammatory response. According to disease severity in individual patients, exacerbations and comorbidities frequently occur. The overall nocturnal and daily symptoms have a strong impact on patient quality of life and clinical outcomes. Bronchodilators, by targeting two important aspects of COPD pathophysiology, ie, bronchoconstriction and lung hyperinflation, are the mainstay of therapy for COPD. Aclidinium bromide in particular is an anticholinergic molecule, approved for maintenance bronchodilator treatment of stable COPD, that combines high antimuscarinic activity with strong kinetic selectivity for the M3 receptor subtype. Moreover, the elevated plasma clearance of aclidinium has been related to low systemic bioavailability and low incidence of anticholinergic adverse events, whereas the reduced residence time at M2 receptors provides good cardiovascular safety. Altogether, these characteristics result in a high safety and tolerability profile. This review aims to reappraise the contribution of symptoms and of the level of quality of life determinants on COPD severity and to evaluate how therapeutic strategies with aclidinium may positively impact on these specific determinants of disease severity.

Analysis of diaphragmatic movement before and after pulmonary rehabilitation using fluoroscopy imaging in patients with COPD.

BACKGROUND: The diaphragm is the principal inspiratory muscle. The purpose of this study was to assess improvements in diaphragmatic movement before and after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), using a fluoroscopy-guided chest X-ray. PATIENTS AND METHODS: Among 117 patients with COPD receiving pulmonary rehabilitation who underwent the initial fluoroscopy-guided chest X-ray and pulmonary function test, 37 of those patients who underwent both initial and follow-up fluoroscopy and pulmonary function tests were enrolled in this study. After hospital education, participants received pulmonary rehabilitation through regular home-based training for at least 3 months by the same physiatrist. We assessed the changes in diaphragm area with fluoroscopy-guided posteroanterior chest X-rays between pre- and postpulmonary rehabilitation. To minimize radiation hazards for subjects, the exposure time for fluoroscopy to take chest X-rays was limited to less than 5 seconds. RESULTS: There were significant improvements (2,022.8±1,548.3 mm(2) to 3,010.7±1,495.6 mm(2) and 2,382.4±1,475.9 mm(2) to 3,315.9±1,883.5 mm(2); right side P=0.001 and left side P=0.019, respectively) in diaphragmatic motion area during full inspiration and expiration in both lungs after pulmonary rehabilitation. Pulmonary function tests showed no statistically significant difference between pre- and postpulmonary rehabilitation. CONCLUSION: The study suggests that the strategy to assess diaphragm movement using fluoroscopy is a relatively effective tool for the evaluation of pulmonary rehabilitation in COPD patients in terms of cost and time savings compared with computed tomography or magnetic resonance imaging.

Significance of Medication History at the Time of Entry into the COPDGene Study: Relationship with Exacerbation and CT Metrics.

BACKGROUND: Despite the importance of respiratory medication use in COPD, relatively little is known about which clinical phenotypes were associated with respiratory medications. METHODS: To determine the association between respiratory medication use and exacerbations or quantitative CT metrics, we analyzed medication history from 4,484 COPD subjects enrolled in the COPDGene Study. RESULTS: 2,941 (65.6%) subjects were receiving one or more respiratory medications; this group experienced more frequent exacerbations in the year before study entry and had increased gas trapping, emphysema, and subsegmental airway wall area, compared to the patients who were on no respiratory medication. In subgroup analysis, subjects who were on triple therapy (long-acting beta2-agonist [LABA], long-acting muscarinic antagonist [LAMA], and inhaled corticosteroids [ICS]) had the highest frequencies of exacerbations and severe exacerbations and tended to have increased quantitative measures of emphysema and gas trapping on CT compared to other five groups. After adjustment for confounding variables, the triple therapy group experienced more exacerbations and severe exacerbations compared with other five groups. In addition, the LABA+LAMA+ICS group was more likely to have emphysema and gas trapping on CT than other groups in multivariable logistic analysis. Interestingly, the total number of respiratory medications was significantly associated with not only the frequency of exacerbations but also gas trapping and airway wall thickness as assessed by CT scan in multivariable analysis. CONCLUSIONS: These results suggest that the use of respiratory medications, especially the number of medications, may identify a more severe phenotype of COPD that is highly susceptible to COPD exacerbations.

Efficacy of diaphragmatic breathing in patients with chronic obstructive pulmonary disease.

This study investigated the effects of diaphragmatic breathing (DB) on ventilation and breathing pattern, seeking to identify predictors of its efficacy in patients with chronic obstructive pulmonary disease (COPD). Twenty-nine patients with moderate and severe COPD were monitored using respiratory inductance plethysmography and metabolic gas analysis. After 4 minutes of natural breathing, subjects completed 2 minutes of DB followed by 4 minutes of natural breathing. Dyspnea was measured using a visual analogue scale. Diaphragmatic mobility was assessed using chest radiography. DB was associated with a significant increase in tidal volume and reduction in breathing frequency, leading to higher ventilation and oxygen saturation, with a reduction in dead space ventilation and ventilatory equivalent for carbon dioxide. A total of 10 subjects with moderate (5) and severe (5) COPD performed DB with asynchronous thoracoabdominal motion, worsening the dyspnea, and decreasing the gain of tidal volume. Diaphragmatic mobility, inspiratory muscular strength, lower scores for dyspnea and hypoxemia as well as coordinated thoracoabdominal motion are associated with effective DB. In patients with COPD, DB can improve breathing pattern and ventilatory efficiency without causing dyspnea in patients whose respiratory muscular system is preserved.

Spinal cord stimulation for severe degenerative joint disease of the shoulder in a patient with severe chronic obstructive pulmonary disease: a new indication?

Approximately 70% of the United States population older than 65 yr has osteoarthritis. Chronic obstructive pulmonary disease (COPD) is also more prevalent in the elderly, and thus, the likelihood of having elderly patients with osteoarthritis and COPD in clinical settings is significant. COPD may preclude the optimum use of opioids, thus the potential to provide pain control with nonpharmacological treatment modalities becomes a valuable option. We present the case of an elderly woman with severe degenerative joint disease of the shoulder and severe COPD in whom spinal cord stimulation was used to provide pain control.