Clinical Characteristics and Health Care Resource Utilization Among Individuals Undergoing Alpha-1 Antitrypsin Testing in a Quaternary Health System.

Relationship between lung function and Modified Shuttle Test performance in adult patients with cystic fibrosis: a cross-sectional, retrospective study

Improvement in postoperative lung function in patients with moderate to severe airway obstruction after robotic-assisted thoracoscopic tracheobronchoplasty.

Timing of quality of life and lung function changes during the first year following lung transplantation: A multicenter prospective cohort study.

<b>Introduction:</b> The course of chronic obstructive pulmonary disease (COPD) is heterogeneous, ranging from stable disease to accelerated deterioration of lung function over time. Exhaustive identification of factors that can predict decline in lung function is still a challenge. <b>Aim of the study:</b> To assess annual decline in forced expiratory volume in 1-second (FEV1) and to identify predictors of lung function deterioration. <b>Methods:</b> In this longitudinal cohort study we enrolled outpatients with stable COPD who were followed up in a tertiary referral center from January 2010 to December 2015. Each participant had at least three spirometries during the study period. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of &lt;0.7 <b>Results:</b> A total of 109 patients with COPD participated (77% male, mean age 67 years). Over a mean follow up of 4 years, 23 patients (21.1%) were hospitalized due to COPD, 39 (35.7 %) experienced more than two exacerbations and 5(4.5%) died. Mean (SE) annual change in FEV1 was - 37.7 ml (13.2).Patients with an estimated decline in FEV1 of more than 40 ml per year (labeled as "decliners"; n=51, 47%), had better lung function at baseline (median baseline FEV1 [IQR]:1260 ml [645] vs 1190 ml [470];p 0.04).Rate of decline in FEV1 was greater in patients with initial GOLD stages I and II (median values [IQR]: -65 ml [159] vs -20 ml [IQR 74];p 0.01) and in those who experienced incident exacerbations ( -75ml [165] vs -33ml [85];p 0.03). Multivariable analysis showed that GOLD stage I-II was a strong independent predictor of FEV1 decline ( RR 4.8, CI 95% 1.07-21.6, p 0.04). <b>Conclusions:</b> These findings strengthen the importance of strict surveillance in the early stages of COPD.

Prolongation of antibiotic treatment for cystic fibrosis pulmonary exacerbations

This issue of the Journal of Gerontology: Medical Sciences highlights new findings on the aging lung and its consequences for health and function (1–6). The aging lung is likely to have experienced frequent and cumulative exposures to environmental toxins, particularly tobacco smoke and respiratory infections, as well as substantial reductions in physiologic capacity (1). As a result, older persons are at an increased risk of developing respiratory impairment, with a wide range of negative consequences that include respiratory symptoms, frailty-related features, disability, and mortality (1). Concurrently, there is an increased prevalence of various pulmonary diseases and cancer in older individuals (2). This issue reviews our current understanding of the diagnostic, epidemiologic, and biologic aspects of the aging lung. In the first article, Vaz Fragoso and Gill (1) propose that respiratory impairment be defined as an age-adjusted reduction in pulmonary function that is independently associated with adverse outcomes. The rationale for this definition is twofold. First, to more accurately establish an underlying respiratory disease, the reduction in pulmonary function must be distinguished from the reduction that is due to normal aging. Second, to avoid inappropriate and potentially harmful pharmacotherapy, as well as delays in the consideration of other diagnoses, the threshold that establishes an age-adjusted reduction in pulmonary function should be linked to adverse outcomes. Using this approach, the authors review the strong evidence that now exists to support the use of spirometric Z-scores as a basis for defining respiratory impairment in older persons. Alternatively, when spirometry is not available or cannot be adequately performed, respiratory impairment may be established by the peak expiratory flow, also expressed as a Z-score. In the second article, Akgun, Crothers, and Pisani (2) review the epidemiology of common pulmonary diseases, namely pneumonia, obstructive lung diseases, idiopathic pulmonary fibrosis, and lung cancer, in older populations. In particular, they review the common clinical presentations for these diseases and highlight differences between younger and older age groups. The risk factors, treatment, and mortality associated with these pulmonary diseases are also discussed, including the relationship with comorbidities, respiratory symptoms, and quality of life. The remaining articles focus on immune-mediated biological mechanisms that potentially underlie the age-related increase in the prevalence of respiratory impairment and pulmonary disease (3–6). Goldstein, for example, reviews the impact of aging on the innate immune response, the first line of defense to pathogen invasion. Based on emerging studies, the author suggests that age-related changes in the innate immune system may contribute to the impaired response to viral infection (3). Of note, from the period 1979 through 2001, persons aged 75 years or more had a 10-fold or greater increase in the rate of influenza-associated hospitalization, relative to any other age group (7). Lee, Shin, and Kang (4) next review the impact of aging on T-cell immunity, as this could lead to an increased vulnerability for developing viral infections, inflammatory diseases (eg, asthma and chronic obstructive lung disease), and malignancies. Based on current evidence, the authors conclude that a range of alterations in T-cell immunity occurs with aging, from cell function to the proportion of T-cell subsets, but that their clinical significance has yet to be elucidated, particularly regarding the aging lung. Jane-Wit and Chun (5) subsequently review the impact of aging on the pulmonary endothelium, as this can lead to infection-related sequelae, a higher prevalence of pulmonary hypertension, and an attenuation of parenchymal healing. Based on current evidence, the authors suggest that the age-related mishandling of intracellular reactive oxygen species, pathologic nitric oxide signaling, and deficient recruitment of stem cell precursors provide a rationale for future therapies that may subvert or even reverse the effects of aging on the respiratory system. Interestingly, studies by Volkova, Zhang, Shaw, and Lee (6) have offered a novel mechanism whereby age-related dysregulation of intracellular reactive oxygen species may occur. They discovered a previously unappreciated role for the innate immune receptor, Toll-like receptor 4 (TLR4), in maintaining an oxidant–antioxidant balance in the lungs and endothelium. They found that mice deficient in TLR4, the canonical receptor for lipopolysaccharide (a component of specific bacteria), exhibit an accelerated form of age-induced lung enlargement that resembles human emphysema, both histologically and functionally (6). Their animal data are supported by recent human studies. As reviewed by Volkova et al., TLR4 function declines with age, which may in part contribute to “senile emphysema” even in the absence of significant exposures (6). Human studies have also found that chronic smoking leads to decreased TLR4 function in the lung and that the level of TLR4 depression is correlated with the severity of chronic obstructive lung disease (8). The synergistic or additive effects of age and smoking on TLR4 function in susceptible individuals may explain the pathogenesis and temporal characteristics of smoke-induced emphysema, which tends to manifest in the latter decades of life despite cessation of smoke exposure. In addition to TLR4, other innate immune receptors are also affected by age and have an important impact on lung disease. In the spirit of “a picture is worth a thousand words,” the very essence of what characterizes an aging lung is best illustrated in Figures 1 and ​and2.2. In the first figure (9), the forced expiratory volume in 1-second—a spirometric measure of pulmonary function—shows a progressive age-related decline across the adult lifespan (top 3 curves), which in vulnerable individuals is substantially accelerated by smoking exposures—a major risk factor for pulmonary disease (bottom curve). In Figure 2, an example is shown of the biology that underlies the increased vulnerability of the aging lung. Specifically, the age-related alterations in innate and adaptive immunity, oxidative stress, endothelial function, and repair processes culminate in dysregulated inflammatory processes and subsequent lung pathology such as infections, airways, interstitial and vascular pulmonary processes, and cancer. Ultimately, it is the interplay of age-related changes in biology and the subsequent responses to environmental exposures that largely define the physiology and clinical presentation of the aging lung. Figure 1. The forced expiratory volume in 1-second (FEV1) across the adult lifespan, in adult males. Reproduced with permission from reference (9). Figure 2. Proposed biologic mechanisms in the aging lung. TLRs = Toll-like receptors; NLRs = Nod-like receptors; RLRs = Rig-I-like receptors; IFN-γ = Interferon-gamma; IL- = Interleukin; ILD = Interstitial lung disease; COPD = Chronic obstructive lung disease; ...

Pulmonary function is not routinely assessed in patients without respiratory disease and symptoms before surgery, even if they are smokers. We aimed to check whether the new spirometric reference values of the worldwide Global Lung Initiative (GLI) affected the preoperative assessment of lung function in allegedly lung-healthy patients compared with the still commonly used old predicted values. Two hundred nineteen allegedly lung-healthy non-smokers, past and current smokers were examined by spirometry before elective surgery. The obtained values of forced expiratory volume in 1second (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC were transformed into z-scores according to the GLI guidelines. A comparison between the new and old reference values was performed. FEV1 was used for the grading of airway obstruction. One hundred eighty-three subjects performed the ventilation manoeuvre according to the GLI recommendations and were analysed. Most non-smokers and past smokers met the new references ranges for spirometric values. Only z-scores of FEV1 /FVC distinguished among all three patient groups, FEV1 between smokers and the other two groups and FVC did not discriminate the groups, irrespective of the reference values used. Airway obstruction was identified in 24% of asymptomatic smokers by z-scores of FEV1 /FVC but in only 14% by the old predicted values. In elderly smokers (>60years), the corresponding values rose to 50% and 30%. Old predicted values of FEV1 underestimated the degree of airway obstruction mainly in middle-aged smokers. Allegedly lung-healthy current smokers showed a higher proportion of preoperatively reduced lung function when z-scores were used, especially in elderly subjects.

Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody that was first approved by the United States (US) Food and Drug Administration (FDA) for the treatment of allergic asthma in 2003. The pivotal trials supporting the initial approval of omalizumab used dosing determined by patient's baseline IgE and body weight, with the goal of reducing the mean free IgE level to approximately 25 ng/mL or less. While the underlying parameters supporting the dosing table remained the same, subsequent studies and analyses have resulted in approved alternative versions of the dosing table, including the European Union (EU) asthma dosing table, which differs in weight bands and maximum allowable baseline IgE and omalizumab dose. In this study, we leveraged modelling and simulation approaches to predict and compare the free IgE reduction and forced expiratory volume in 1second (FEV1) improvement with omalizumab dosing based on the US and EU asthma dosing tables. Previously established population pharmacokinetic-IgE and IgE-FEV1 models were used to predict and compare post-treatment free IgE and FEV1 based on the US and EU dosing tables. Clinical trial simulations (with virtual asthma populations) and Monte Carlo simulations were performed to provide both breadth and depth in the comparisons. The US and EU asthma dosing tables were predicted to result in generally comparable free IgE suppression and FEV1 improvement. Despite the similar free IgE and FEV1 outcomes from simulations, this has not been clinically validated with respect to the registrational endpoint of reduction in annualized asthma exacerbations.

RATIONALE: Race-specificGlobal Lung Initiative (GLI) equations for lung function rely on non-evidence-basedassumptions of biological differences between races. In 2023, the AmericanThoracic Society (ATS) recommended using race-neutral reference equations andre-evaluating pulmonary function tests (PFTs) in clinical settings. However, race-neutral equations may disproportionately exclude more Black patients frompotentially curative lung resection surgery. While race-specific equations mayunderestimate risk, masking compromised lung function and leading to worsepost-operative functional status. Our study examines the impact ofrace-specific versus race-neutral equations on resection risk, based on FEV1%predicted for assumed 1, 3, and 5 segment resections. METHODS: This single-center retrospective chart review was conducted at an urbanVeterans Health Administration Medical Center. We identified patients screenedwith low-dose CT for lung cancer and later diagnosed with non-small cell lungcancer from 1/1/2016 – 6/30/2024. We obtained the forced expiratory volume in 1second (FEV1) and diffusion capacity (DLCO) from most recent pulmonary functiontests (PFTs) prior to cancer diagnosis. Usingthe segment counting method, we calculated predicted postoperative (PPO) FEV1and DLCO for 1, 3, and 5 segment resections with the formula: PPO FEV1 =preoperative FEV1 x (1 – a/b), where “a” is the number of segments tobe resected and “b” is the total number of segments (assume 19). FEV1% predicted was calculated with GLIrace-specific and GLI Global/Mixed (race-neutral) reference equations, whileDLCO was calculated using GLI. We stratified risk as follows: ≥80% (no risk), ≥40-&amp;lt;80%(further testing), and &amp;lt;40% (very high risk). RESULTS: A total of 113patients were included (96% male; 75% &amp;gt;65 years). Of these, 84 (74.3%) wereBlack, 28 (24.8%) Caucasian, and 1 classified as ‘other’. Among Black patients,8 (7.0%) were reclassified from ‘no surgical risk’ to ‘further testing’ whenusing race-neutral instead of race-specific equations. Additionally, 4 patients(3.5%) were reclassified from ‘further testing’ to ‘very high risk’ for1-segment resection, 4 (3.5%) for 3-segment resection, and 1 (0.9%) for5-segment resection. Notably, 7 of the 9 patients reclassified to ‘very highrisk’ already had DLCO &amp;lt;40%, indicating already high surgicalrisk. CONCLUSION: Using race-neutral equations, only 7% of Blackpatients reclassified from ‘no risk’ to ‘further testing,’ potentially allowingfor better risk management. A smaller proportion reclassified from ‘furthertesting’ to ‘very high risk’ after accounting for 1, 3, and 5 segmentresections, with most already classified as high risk due to DLCO.

Changes in pulmonary function of residents in Sanriku Seacoast following the tsunami disaster from the Great East Japan Earthquake.

Introduction: Dysanapsis refers to a developmental mismatch between airway tree caliber and lung size. Smaller airway tree caliber relative to total lung volume (TLV) assessed by computed tomography (CT) is associated with obstructive lung physiology, but whether this association is related to smaller airways, larger lungs or both, is uncertain. This study investigated the association of CT-assessed airway-to-lung ratio (ALR) and its structural components-airway tree caliber and TLV- with indices of obstructive lung physiology at rest and peak exercise. Methods: CanCOLD is a population-based cohort of adult non-smokers and smokers with or without COPD that underwent full-lung CT, spirometry, plethysmography, and symptom-limited incremental cardiopulmonary exercise testing to assess peak rate of oxygen uptake (V'O2peak), with inspiratory capacity (IC) maneuvers, and ratio of exertional dyspnea (Borg 0-10)-to-minute ventilation (V'E).Mean airway tree caliber, TLV, and ALR were quantified by CT (VIDA Diagnostics). Spirometric airflow obstruction severity was quantified using forced expiratory volume in 1-second (FEV1). ERS/ATS spirometry-defined dysanapsis required a pre-bronchodilator FEV1:forced vital capacity&amp;lt;lower limit of normal (LLN) and FEV1&amp;gt;LLN. Dynamic hyperinflation (DH) required an IC decrement from rest-to-peak exercise&amp;gt;0.15L. Regression models adjusted for sex, age, age2, height and height2. Results: Among 161 non-smoking non-asthmatic participants with airflow obstruction (pre-bronchodilator FEV1/FVC&amp;lt;0.7 (mean±SD age: 69±10 years, 34% female), smaller ALR was associated with smaller airway tree caliber (p&amp;lt;0.001) and larger TLV (p&amp;lt;0.001, Table). When partitioning smaller ALR into its components, smaller airway tree caliber was associated with lower FEV1 (p=0.001), greater dyspnea:V'E (p=0.015), and more DH (p=0.016), but not lower V'O2peak (p=0.234); whereas, larger TLV was associated with higher FEV1 (p&amp;lt;0.001), and higher V'O2peak (p=0.002), but not DH (p=0.882) or dyspnea:V'E (p=0.079). ERS/ATS-defined spirometric dysanapsis was associated with the larger TLV (p=0.003) but not smaller airway tree caliber (p=0.264) etiotype of dysanapsis. Results tended to remain consistent when restricting to those with a post-bronchodilator FEV1/FVC&amp;lt;0.7 (n=114) or pre-bronchodilator FEV1/FVC&amp;lt;LLN (n=89). Conclusion: When partitioning ALR into its structural components among non-smoking non-asthmatic participants with airflow obstruction, smaller airway tree caliber was associated with obstructive lung physiology, whereas larger TLV was associated with better spirometry and higher V'O2peak. The ERS/ATS spirometry-based definition of dysanapsis identified a larger proportion of individuals with larger TLV rather than smaller airway tree caliber. Our observations suggest that not all pathways to dysanapsis are equivalent with respect to obstructive physiology, which may have implications for spirometry-based definitions of dysanapsis.

The aims of this study were to evaluate the role of high resolution computed tomography of the thorax in detecting abnormalities in chronic asthmatic patients and to determine the behavior of these lesions after at least one year. Fourteen persistent asthmatic patients with a mean forced expiratory volume in 1-second that was 63% of predicted and a mean forced expiratory volume in 1-second /forced vital capacity of 60% had two high resolution computed tomographies separated by an interval of at least one year. All 14 patients had abnormalities on both scans. The most common abnormality was bronchial wall thickening, which was present in all patients on both computed tomographies. Bronchiectasis was suggested on the first computed tomography in 5 of the 14 (36%) patients, but on follow-up, the bronchial dilatation had disappeared in 2 and diminished in a third. Only one patient had any emphysematous changes; a minimal persistent area of paraseptal emphysema was present on both scans. In 3 patients, a "mosaic" appearance was observed on the first scan, and this persisted on the follow-up computed tomography. Two patients had persistent areas of mucoid impaction. In a third patient, mucus plugging was detected only on the second computed tomography. We conclude that there are many abnormalities on the high resolution computed tomography of patients with persistent asthma. Changes suggestive of bronchiectasis, namely bronchial dilatation, frequently resolve spontaneously. Therefore, the diagnosis of bronchiectasis by high resolution computed tomography in asthmatic patients must be made with caution, since bronchial dilatation can be reversible or can represent false dilatation. Nonsmoking chronic asthmatic subjects in this study had no evidence of centrilobular or panacinar emphysema.

The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross-sectional and longitudinal analysis. Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3years' follow-up were included. In cross-sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching. Of 11892 eligible participants (mean age, 47.7years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross-sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1-second (men, 3.52 vs 3.44L, P<.001; women, 2.62 vs 2.45L, P<.001) and forced vital capacity (men, 4.33 vs 4.24L, P<.001; women, 3.11 vs 2.97L, P<.001) than the control group. In longitudinal analysis, during the mean follow-up period of 6.6years, there were no significant differences in forced expiratory volume in 1-second or forced vital capacity decline rates between two groups in the propensity score-matched cohorts (n=4558). However, those with high nonalcoholic fatty liver disease fibrosis score and fibrosis-4 (men, -21.7 vs -27.4mL/y, P=.001; women, -22.4 vs -27.9mL/y, P=.016) showed significantly faster decline in forced vital capacity compared to those with low scores. Nonalcoholic fatty liver disease was associated with decreased lung function at baseline but was not associated with accelerated lung function decline in the propensity score-matched cohort. However, hepatic fibrosis was significantly associated with rapid forced vital capacity decline.

Previous investigations of workers exposed to machining fluids have shown increased rates of cough and phlegm and have shown that these exposures may cause occupational asthma. To examine acute responses to these agents, cross-shift lung function changes related to machining fluid aerosols among 89 machine operators at two factories producing automobile parts were measured and compared with the findings for 42 unexposed assembly workers studied similarly at the same factories. Workers wore a personal air-sampling device on a Monday and Friday of a working week, and spirometry was performed before and after the work shifts on both days. On Mondays, a 5% or greater decrease in the forced expiratory volume in 1-second (FEV1), regarded as an "FEV1-response," occurred in 23.6% of the machinists and in only 9.5% of the assembly workers (relative risk = 2.5, p less than .05). After adjusting statistically for a history of childhood asthma, for smoking prior to lung function testing, and for race, odds ratios for an FEV1-response of 4.4 among workers exposed to aerosols of straight mineral oils, 5.8 for oil emulsions, and 6.9 for synthetic fluids were found. The FEV1-responses on Fridays were similar to those on Mondays. There was no progressive decline in FEV1 over the work week. Personal air samples, collected with a two-stage impactor, allowed aerosol masses to be measured in three size fractions: less than 3.5 microns, 3.5-9.8 microns, and greater than 9.8 microns aerodynamic diameter. Exposure levels to each type of machining fluid were remarkably similar within each size fraction and for total aerosol levels. Total aerosol concentrations for assembly workers ranged from 0.07 to 0.44 mg/M3, and for machinists from 0.16 to 2.03 mg/m3. Inhalable particle (less than or equal to 9.8 microns) levels were derived from the sum of the air concentrations in the two smallest-size fractions, and significant cross-shift decrements in FEV1 on Mondays and Fridays were associated with inhalable aerosol levels greater than 0.20 mg/m3. These findings show that acute airflow obstruction is associated with exposures to aerosols of various machining fluids and that airway responses occur well below current recommended exposure limits.

Multiple antibiotic-resistant Pseudomonas aeruginosa and lung function decline in patients with cystic fibrosis