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Objectives: Inspiratory muscle training is used in rehabilitation to exercise respiratory muscles in various conditions associated with limited ventilatory reserve. In this review, we investigated inspiratory muscle training in lung transplant candidates and recipients., Materials and Methods: We searched 5 primary databases from inception through April 2024. Two key word entries, "lung transplantation" and "inspiratory muscle training," were matched using the Boolean operator AND. No filters were applied for document type, age, sex, publication date, language, and subject., Results and Conclusions: The searched databases returned 119 citations. Seven articles that considered 64 patients (47% female) were included in the final analysis, with 1 study involving a pediatric patient. Lung transplant recipients used a threshold trainer at 15% to 60% of maximal inspiratory pressure and mostly exercised twice daily for 10 to 15 minutes per session. Lung transplant candidates exercised at 30% to >50% of maximal inspiratory pressure twice daily, performing 30 to 60 inspirations or for 15 minutes. The highest inspiratory muscle strength was observed in a series of adult lung transplant recipients whose mean value improved by 31.8 ± 14.6 cmH2O versus baseline after treatment. To the same extent, the highest value of maximal inspiratory pressure was detected in a pediatric patient who scored 180 cmH2O after training. Overall, participants obtained improvements in lung function (forced expiratory volume in 1 second, forced vital capacity), functional performance, dyspnea intensity, and exercise tolerance. Inspiratory muscle training is easy to perform and can be done at home without specific supervision (in adults) before or after a lung transplant. Nevertheless, additional rigorous investigations should aim to replicate the positive effects reported in the present review.

Background: Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts., Methods: We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use., Results: Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time., Conclusion: We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Background: Helicobacter pylori (HP) infection is associated with reduced lung function and systemic inflammation in chronic obstructive pulmonary disease (COPD) patients. Azithromycin (AZ) is active against HP and reduces the risk of COPD exacerbation. We determined whether HP infection status modifies the effects of AZ in COPD patients., Methods: Plasma samples from 1018 subjects with COPD who participated in the Macrolide Azithromycin (MACRO) in COPD Study were used to determine the HP infection status at baseline and 12 months of follow-up using a serologic assay. Based on HP infection status and randomization to either AZ or placebo (PL), the subjects were divided into 4 groups: HP+/AZ, HP-/AZ, HP+/PL, and HP-/PL. Time to first exacerbation was compared across the 4 groups using Kaplan-Meier survival analysis and a Cox proportional hazards model. The rates of exacerbation were compared using both the Kruskal-Wallis test and negative binomial analysis. Blood biomarkers at enrolment and at follow-up visits 3, 12, and 13 (1 month after treatment was stopped) months were measured., Results: One hundred eighty one (17.8%) patients were seropositive to HP. Non-Caucasian participants were nearly three times more likely to be HP seropositive than Caucasian participants (37.4% vs 13.6%; p < 0.001). The median time to first exacerbation was significantly different across the four groups (p = 0.001) with the longest time in the HP+/AZ group (11.2 months, 95% CI; 8.4-12.5+) followed by the HP-/AZ group (8.0 months, 95% CI; 6.7-9.7). Hazard ratio (HR) for exacerbations was lowest in the HP+/AZ group after adjustment for age, sex, smoking status, ethnicity, history of peptic ulcer, dyspnea, previous hospital admission, GOLD grade of severity, and forced vital capacity (HR, 0.612; 95% CI, 0.442-0.846 vs HR, 0.789; 95% CI, 0.663-0.938 in the HP-/AZ group). Circulating levels of soluble tumor necrosis factor receptor-75 were reduced only in the HP+/AZ group after 3 months of AZ treatment (-0.87 ± 0.31 μg/L; p = 0.002); levels returned to baseline after discontinuing AZ., Conclusions: AZ is effective in preventing COPD exacerbations in patients with HP seropositivity, possibly by modulating TNF pathways related to HP infection.

Background: Donor-to-recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT)., Methods: We calculated the pTLC ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between March 2002 to December 2010. Patients were stratified by pTLC ratio >1.0 ("oversized") and pTLC ratio ≤1.0 ("undersized"). PGD was defined as any ISHLT Grade 3 PGD (PGD3) within 72 hours of reperfusion. We analyzed the association between risk factors and PGD using multivariable conditional logistic regression. As transplant diagnoses can influence the size-matching decisions and also modulate the risk for PGD, we performed pre-specified analyses by assessing the impact of lung size mismatch within diagnostic categories., Results: In univariate analyses oversizing was associated with a 39% lower odds of PGD3 (OR 0.61, 95% CI, 0.45-0.85, p = 0.003). In a multivariate model accounting for center-effects and known PGD risks, oversizing remained independently associated with a decreased odds of PGD3 (OR 0.58, 95% CI 0.38 to 0.88, p = 0.01). The risk-adjusted point estimate was similar for the non-COPD diagnosis groups (OR 0.52, 95% CI 0.32 to 0.86, p = 0.01); however, there was no detected association within the COPD group (OR 0.72, 95% CI 0.29 to 1.78, p = 0.5)., Conclusion: Oversized allografts are associated with a decreased risk of PGD3 after BLT; this effect appears most apparent in non-COPD patients., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic pulmonary arterial hypertension (IPAH) is associated with high short-term mortality after bilateral lung transplantation (BLT). Previous studies have suggested that oversized allografts are associated with improved outcomes and that this association was strongest within the first year after transplant. We hypothesized that oversizing the allograft is associated with improved survival after BLT for IPAH., Methods: All adults in the United Network of Organ Sharing lung transplant registry who underwent first-time BLT for IPAH between October 1989 and April 2010 were studied. Lung size mismatch was assessed by calculating the predicted total lung capacity (pTLC) ratio of the donor to the recipient. The cohort was divided evenly into "undersized" (pTLC ratio less than the median pTLC ratio) and "oversized" (pTLC ratio exceeding the median pTLC ratio). Risk of death after BLT was analyzed using Kaplan-Meier survival and Cox proportional hazards models., Results: The mean pTLC ratio was 0.93 ± 0.10 in the 302 undersized patients compared with 1.24 ± 0.14 in the 302 oversized patients. Cohorts had comparable baseline characteristics. Median survival was 831 days longer in the oversized cohort (2,166 vs. 1,335 days, p = 0.006). In a multivariate model controlling for sex mismatch, recipient factors, acuity, donor factors, and transplant factors, oversizing was associated with decreased hazard for death at 5 years (hazard ratio, 0.73; 95% CI 0.56-0.96, p = 0.02)., Conclusion: Oversizing the allograft is associated with improved survival after BLT for IPAH. In the setting of donor organ shortages and waiting list mortality, it is not practical to intentionally oversize the allograft. However, the pTLC ratio could provide further refinement in the peri-transplant risk assessment., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Rationale: The association between a high predicted total lung capacity (pTLC) ratio (equal to pTLC(donor)/pTLC(recipient)), suggestive of an oversized allograft, with improved survival after lung transplantation (LTx) remains controversial., Objectives: To characterize donor-recipient lung size matching based on the pTLC ratio and to investigate the relationship of the pTLC ratio with post-LTx survival., Methods: All subjects in the Scientific Registry of Transplant Recipients, who underwent first-time LTx in the lung allocation score-based system between May 4, 2005 and March 31, 2012, were studied, and the pTLC ratio was calculated on the basis of sex, height, and age. Risk of death after LTx was analyzed using Cox proportional hazards models., Measurements and Main Results: The pTLC ratio was available for 10,289 of the 10,318 study subjects (99.7%). The mean pTLC ratio was 1.015 ± 0.175 (interquartile range, 0.918-1.119). Univariate analysis showed that the pTLC ratio was strongly associated with death in the first LTx year (P < 0.0001). With the pTLC ratio entered as a spline there was a nonlinear association with declining risk of death with higher pTLC ratio from 0.5 to about 1.3, where an inflection occurred with rising risk at higher values. Accounting for the pTLC ratio, recipient and donor sex were not independently associated with death after LTx. A change of pTLC ratio from 0.918 to 1.119 (the interquartile range) was associated with similar point estimates of reduced risk of death at 1 year in univariate (hazard ratio, 0.78) and comprehensive risk-adjusted multivariate models (hazard ratio, 0.86)., Conclusions: The pTLC ratio is an independent predictor of death in the first year after LTx and explains the association of sex with survival after LTx. Incorporating the pTLC ratio in the lung allocation mechanism could improve outcomes after LTx.

Objectives: Mechanical ventilation tidal volumes are usually set according to an estimate of patient size in millilitres (ml) per kilogram (kg) body weight. We describe the relationship between donor-recipient lung-size mismatch and postoperative mechanical ventilation tidal volumes according to recipient- and donor-predicted body weights in a cohort of bilateral lung transplant patients., Methods: A most-undersized (10 patients with lowest predicted total lung capacity [pTLC] ratio = pTLC-donor/pTLC-recipient), a most-oversized (10 patients with highest pTLC ratio) and best-matched subset (10 patients with predicted total lung capacity ratio closest to 1.0) were selected within a cohort of 70 patients. All tidal volumes during mechanical ventilation in the first 96 h after bilateral lung transplantation were recorded. Tidal volumes were expressed in ml and ml/kg-recipient-predicted body weights and ml/kg-donor-predicted body weights., Results: Postoperative absolute tidal volumes (in ml) were comparable between subsets of patients with undersized, matched and oversized allografts (552 ± 103 vs 581 ± 107 vs 582 ± 104 ml), and tidal volumes in ml/kg-recipient-predicted body weights were also similar (8.8 ± 1.4 vs 9.3 ± 1.1 vs 9.8 ± 2.1). However, tidal volumes in ml/kg-donor-predicted body weights revealed significant differences between undersized, matched, and oversized subsets (11.4 ± 3.1 vs 9.4 ± 1.2 vs 8.1 ± 2.1, respectively; P < 0.05). Two patients developed primary graft dysfunction grade 3, both in the undersized subset. Four patients in the undersized group underwent tracheotomy (vs none in matched and one in oversized subset)., Conclusions: During mechanical ventilation after bilateral lung transplantation, undersized allografts received relatively higher tidal volumes compared with oversized allografts when the tidal volumes were related to donor-predicted body weights.

Background: The purpose of this study was to investigate the relationship between donor-recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival., Methods: The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio ≤1.0 or >1.0 and height ratio ≤1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models., Results: There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival., Conclusions: A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft-thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Oversizing the lung allograft, as estimated by a donor-to-recipient predicted total lung capacity (pTLC) ratio > 1.0, was associated with improved long-term survival after lung transplantation (LTx) but could be associated with increased post-operative complications and higher resource utilization., Methods: The prospectively maintained LTx database at The Johns Hopkins Hospital was retrospectively reviewed for bilateral LTx patients in the post-Lung Allocation Score (LAS) era. Patients were grouped by pTLC ratio ≤ 1.0 (undersized) or > 1.0 (oversized). Post-operative complications and hospital charges were analyzed., Results: The pTLC ratio was available for 70 patients: 31 were undersized and 39 oversized. Undersized patients had a higher LAS (40.4 vs 35.8, p = 0.009), were more often in the intensive care unit (ICU) pre-LTx (35% vs 10%, p = 0.01), and had a higher occurrence of primary graft dysfunction (PGD; 25% vs 5%, p = 0.013) and tracheostomy (32% vs 10%, p = 0.02), longer index hospitalizations (20 [interquartile range (IQR), 10-46] vs 16 [IQR, 12-25] days, p = 0.048), and higher index hospitalization charges ($176,247 [IQR, $137,646-$284,012] vs $158,492 [IQR, $136,250-$191,301], p = 0.04). After adjusting for LAS and pre-LTx ICU stay, a lower pTLC ratio remained associated with higher hospital charges (p = 0.049). Airway complications were more frequent and severe in undersized patients., Conclusion: Oversized allografts were not associated with an increase in post-LTx complications. However, LTx recipients of undersized allografts were more likely to experience PGD, tracheostomy, and had higher resource utilization. Higher acuity in the undersized group might explain these findings; however, multivariate models suggest an independent association between undersizing, PGD, and resource utilization., (Published by Elsevier Inc.)

Background: Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil., Methods: A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC / recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio ≤ 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function., Results: The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 ± 0.13 vs 0.89 ± 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV(1)/FVC ratios (0.895 ± 0.13 vs 0.821 ± 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 ± 0.2 vs 0.64 ± 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% ± 17.1% vs 65.3% ± 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome (BOS) showed that patients in the oversized cohort had a lower probability of BOS (P < .001)., Conclusions: A pTLC ratio > 1.0, suggestive of an oversized allograft, is associated with higher expiratory airflow capacity and a less frequent occurrence of BOS.