Fibroblast Growth Factor 23 is Associated with a Frequent Exacerbator Phenotype in COPD: A Cross-Sectional Pilot Study.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory airway disease punctuated by exacerbations (AECOPD). Subjects with frequent AECOPD, defined by having at least two exacerbations per year, experience accelerated loss of lung function, deterioration in quality of life and increase in mortality. Fibroblast growth factor (FGF)23, a hormone associated with systemic inflammation and altered metabolism is elevated in COPD. However, associations between FGF23 and AECOPD are unknown. In this cross-sectional study, individuals with COPD were enrolled between June 2016 and December 2016. Plasma samples were analyzed for intact FGF23 levels. Logistic regression analyses were used to measure associations between clinical variables, FGF23, and the frequent exacerbator phenotype. Our results showed that FGF23 levels were higher in frequent exacerbators as compared to patients without frequent exacerbations. FGF23 was also independently associated with frequent exacerbations (OR 1.02; 95%CI 1.004-1.04; p = 0.017), after adjusting for age, lung function, smoking, and oxygen use. In summary, FGF23 was associated with the frequent exacerbator phenotype and correlated with number of exacerbations recorded retrospectively and prospectively. Further studies are needed to explore the role of FGF 23 as a possible biomarker for AECOPD to better understand the pathobiology of COPD and to help develop therapeutic targets.

Diffuse pulmonary ossification: A case report unveiling clinical and histopathological challenges.

Diffuse pulmonary ossification (DPO) is a rare pulmonary condition characterized by the diffuse formation of mature bone in the lungs. Pulmonary ossification, in general, can be subdivided into diffuse pulmonary ossification (DPO) and nodular pulmonary ossification (NPO). DPO occurs most commonly in the settings of chronic pulmonary conditions; however, idiopathic cases have been reported. We present a case of DPO in a 36-year-old man with progressive exertional dyspnea, productive cough, and occasional hemoptysis. Imaging studies showed innumerable pulmonary nodules scattered throughout both lungs. Initially, the diagnoses of pulmonary alveolar microlithiasis (PAM) or, less likely miliary tuberculosis (TB) were considered. However, Quantiferon TB test was negative and genetic testing was negative for SLC34A2, lowering the probability of PAM. The patient underwent a segmentectomy. Microscopic examination showed ramifying spicules of mature woven bone and fatty marrow consistent with DPO. There were no significant underlying pathologic findings, such as interstitial fibrosis, granulomas, organizing pneumonia, or significant inflammation in the background lung parenchyma. In conclusion, clinicians and radiologists need to be aware of DPO in the differential diagnosis of miliary tuberculosis and pulmonary alveolar microlithiasis. The absence of an underlying chronic pulmonary condition does not exclude the possibility of DPO.

Decrease in Exacerbations During the Coronavirus Disease 2019 Pandemic in a Cohort of Veterans with COPD.

BACKGROUND: Studies have shown a decline in hospitalizations due to acute exacerbations of COPD (AECOPD) during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic in AECOPD of all severities in longitudinal cohorts of patients is lacking. METHODS: We conducted analysis of 123 individuals with COPD who have been followed since 2017. AECOPDs of mild (treatment at home), moderate (emergency department or urgent visit evaluation), and severe (hospitalization) type were assessed by chart review and patient interview. Compliance with preventive measures to avoid COVID-19 infection was assessed in 2020. Differences between the rate of AECOPD by year was analyzed as well as differences in preventive measures by COPD disease severity. RESULTS: During the COVID-19 pandemic in 2020, there was a significant reduction in AECOPDs in our cohort with 26 participants (21%) having an exacerbation compared to 46 (37%) in 2019, 52 (42%) in 2018, and 44 (36%) in 2017. Mean exacerbation rates decreased 54% overall and 74% in frequent exacerbators compared with the prior 3-year average. The decrease was noted in AECOPDs of all severities. Overall, there was a high rate of reported compliance with social distancing and face mask use that was significantly higher in the group with more severe COPD based on symptoms and forced expiratory volume in 1 second. CONCLUSIONS: Individuals with COPD, including frequent exacerbators, showed a marked decrease in AECOPD during the COVID-19 pandemic and high adherence to recommended preventive measures. Evaluation of the impact of preventive strategies on AECOPD in a non-pandemic setting may be of value and requires further study.

Beyond inspiratory muscle strength: Clinical utility of single-breath work capacity assessment in veterans with COPD.

BACKGROUND: Inspiratory muscle function in COPD has been traditionally described in terms of maximal inspiratory pressure (MIP). Arguably, however, is the day-to-day relevance of MIP, given that individuals rarely need maximal inspiratory forces to perform general tasks, but rather repeated breathing muscle contractions which demand endurance. The sustained maximal inspiratory pressure (SMIP) reflects the ability of the respiratory muscles to maintain force over time (i.e. single-breath work capacity). We investigated the relationships between SMIP and COPD-related clinical outcomes, hypothesizing that SMIP would have superior correlational and discriminatory value when compared to MIP. METHODS: 61 males with mild-to-very severe airflow obstruction underwent measures of spirometry, whole-body plethysmography, symptomatology, comorbidity, quality of life, exacerbations and mental health. MIP and SMIP were obtained via the Test of Incremental Respiratory Endurance. RESULTS: The mean ±â€¯SD MIP and SMIP were 77.2 ±â€¯22.9 cmH2O and 407.9 ±â€¯122.8 PTU. Both MIP and SMIP positively correlated with pulmonary function, with SMIP displaying the highest correlations. We found significant differences in spirometry, hyperinflation, symptomatology, exacerbation frequency, comorbidity, quality of life and anxiety in subjects grouped as having reduced or normal single-breath work capacity. Finally, significantly lower SMIP values were found in individuals with an IC/TLC ratio ≤25%. CONCLUSIONS: The assessment of SMIP appears to have superior clinical value than MIP in COPD. Our analyses revealed that subjects whose SMIP was reduced experienced more severe airflow obstruction, greater hyperinflation, as well as worse health and mental status with increased symptomatology and impaired quality of life.

Higher serum levels of systemic inflammatory markers are linked to greater inspiratory muscle dysfunction in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an inflammatory response that becomes more pronounced in acute exacerbations. Considerable attention has recently focused on the value of several inflammatory mediators in predicting worsening of COPD-related symptoms. Whereas respiratory muscle dysfunction is also widely present in this population, little is known about how systemic inflammation relates to inspiratory muscle dysfunction in COPD. METHODS: Fifty-three males with mild-to-very severe airflow obstruction underwent blood sampling for 23 inflammatory markers, including acute-phase proteins, cytokines and adipokines. Inspiratory muscle performance was assessed via the test of incremental respiratory endurance, providing measures of maximal (MIP) and sustained maximal (SMIP) inspiratory pressures. RESULTS: The mean ± SD MIP and SMIP were 75.32 ± 19.62 cmH2 O and 406.15 ± 124.55 PTU. MIP negatively correlated with CRP, SAA and cystatin C (r-values from -0.333 to -0.378, P < 0.02), while SMIP was inversely related to SAA and cystatin C (r = -0.534 and r = -0.396, P = 0.00). Significant differences in CRP, SAA, cystatin C and PARC were also found between subjects with and without inspiratory muscle weakness. No additional significant relationships were observed between either MIP or SMIP and other inflammatory markers in the study. CONCLUSIONS: MIP and SMIP are markedly reduced with greater degrees of inflammation in COPD as expressed by higher levels of CRP, SAA and cystatin C. Future research is needed to further examine the above findings and determine the impact of systemic inflammation along with its underlying mechanisms on inspiratory muscle function in COPD.

The BODE index and inspiratory muscle performance in COPD: Clinical findings and implications.

OBJECTIVES: The Test of Incremental Respiratory Endurance is a novel testing method that provides a unique examination of one's inspiratory muscle strength, work and endurance. Little is known about the relationship between inspiratory muscle performance and mortality risk in obstructive lung disease. We examined the relationship between the Test of Incremental Respiratory Endurance measures and the Body-mass index, airflow Obstruction, Dyspnea and Exercise index in chronic obstructive pulmonary disease. METHODS: In all, 70 males with mild-to-very severe chronic obstructive pulmonary disease (mean ± standard deviation of 70.2 ± 5.9 years) underwent measurements of body-mass index, spirometry, dyspnea and a 6-min walk test from which the Body-mass index, airflow Obstruction, Dyspnea and Exercise score was calculated. The Test of Incremental Respiratory Endurance provided measures of maximal inspiratory pressure, sustained maximal inspiratory pressure and inspiratory duration. RESULTS: All Test of Incremental Respiratory Endurance parameters inversely correlated with the Body-mass index, airflow Obstruction, Dyspnea and Exercise score: maximal inspiratory pressure (r = -0.355, p = 0.00), sustained maximal inspiratory pressure (r = -0.426, p = 0.00) and ID (r = -0.278, p = 0.02), with sustained maximal inspiratory pressure displaying the highest correlation. Independent significant correlations were also observed between the sustained maximal inspiratory pressure and all Body-mass index, airflow Obstruction, Dyspnea and Exercise score components, except for body-mass index. Finally, sustained maximal inspiratory pressure was significantly different among the Body-mass index, airflow Obstruction, Dyspnea and Exercise index quartiles. DISCUSSION: The significant association between the Body-mass index, airflow Obstruction, Dyspnea and Exercise score and inspiratory muscle performance, in particular sustained maximal inspiratory pressure, suggests that these measures may have a potential prognostic value in the evaluation of chronic obstructive pulmonary disease.

Reliability and validity of the test of incremental respiratory endurance measures of inspiratory muscle performance in COPD.

Purpose: The Test of Incremental Respiratory Endurance (TIRE) provides a comprehensive assessment of inspiratory muscle performance by measuring maximal inspiratory pressure (MIP) over time. The integration of MIP over inspiratory duration (ID) provides the sustained maximal inspiratory pressure (SMIP). Evidence on the reliability and validity of these measurements in COPD is not currently available. Therefore, we assessed the reliability, responsiveness and construct validity of the TIRE measures of inspiratory muscle performance in subjects with COPD. Patients and methods: Test-retest reliability, known-groups and convergent validity assessments were implemented simultaneously in 81 male subjects with mild to very severe COPD. TIRE measures were obtained using the portable PrO2 device, following standard guidelines. Results: All TIRE measures were found to be highly reliable, with SMIP demonstrating the strongest test-retest reliability with a nearly perfect intraclass correlation coefficient (ICC) of 0.99, while MIP and ID clustered closely together behind SMIP with ICC values of about 0.97. Our findings also demonstrated known-groups validity of all TIRE measures, with SMIP and ID yielding larger effect sizes when compared to MIP in distinguishing between subjects of different COPD status. Finally, our analyses confirmed convergent validity for both SMIP and ID, but not MIP. Conclusion: The TIRE measures of MIP, SMIP and ID have excellent test-retest reliability and demonstrated known-groups validity in subjects with COPD. SMIP and ID also demonstrated evidence of moderate convergent validity and appear to be more stable measures in this patient population than the traditional MIP.