Effects of a cardiopulmonary rehabilitation protocol on functional capacity, dyspnea, fatigue, and body composition in individuals with post-COVID-19 syndrome: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Reduced functional capacity, dyspnea, fatigue, and changes in body composition are common in patients with post-COVID-19 syndrome (PCS), and cardiopulmonary rehabilitation may improve these parameters. Thus, the present study verified the effects of cardiopulmonary rehabilitation (respiratory, aerobic, and resistance muscle training) on submaximal exercise tolerance, dyspnea, fatigue, and body composition. METHODS: This controlled and randomized clinical trial applied a six-week outpatient intervention protocol in individuals over 18 years old (n = 33) with a diagnosis of COVID-19 confirmed by polymerase chain reaction. These individuals were allocated to cardiopulmonary rehabilitation (n = 17) or control groups (i.e., educational lectures; n = 16). The cardiopulmonary rehabilitation group performed respiratory, aerobic, and resistance muscle training. Submaximal exercise tolerance, dyspnea, fatigue, and body composition were assessed before and after the protocol. RESULTS: After 6 weeks, the cardiopulmonary rehabilitation group increased the tolerance to submaximal exercise, with a difference of 100.46 m (95% confidence interval [CI]: 7.40-193 m) in the distance walked on the six-minute walk test, reduced dyspnea (-1.45, 95% CI: -1.98--0.92) in the modified Medical Research Council, and increased 0.63 kg (95% CI: 0.09-1.18 kg) of muscle mass in the upper limbs compared with the control group. CONCLUSION: The six-week cardiopulmonary rehabilitation protocol improved functional capacity, reduced dyspnea, and increased muscle mass in the upper limbs in individuals with PCS. Thus, these results supported the protocol use in this population and encourage further studies to assess its effectiveness in a large sample.

Abnormal heart rate responses to exercise in non-severe COPD: relationship with pulmonary vascular volume and ventilatory efficiency.

BACKGROUND: Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics. METHODS: This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET. RESULTS: We included 49 patients with FEV1 of 1.2-5.0 L (51.1-129.7%), 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [95% CI], 7.26 [1.56-33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [95% CI], 10.67 [2.23-51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [95% CI], 11.46 [2.03-64.89], nadir VE/VCO2 ≥ median; OR [95% CI], 6.36 [1.18-34.42]). CONCLUSIONS: Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.

Effects of three weeks base training at moderate simulated altitude with or without hypoxic residence on exercise capacity and physiological adaptations in well-trained male runners.

Objectives: To test the hypothesis that 'live high-base train high-interval train low' (HiHiLo) altitude training, compared to 'live low-train high' (LoHi), yields greater benefits on performance and physiological adaptations. Methods: Sixteen young male middle-distance runners (age, 17.0 ± 1.5 y; body mass, 58.8 ± 4.9 kg; body height, 176.3 ± 4.3 cm; training years, 3-5 y; training distance per week, 30-60 km.wk-1) with a peak oxygen uptake averaging ~65 ml.min-1.kg-1 trained in a normobaric hypoxia chamber (simulated altitude of ~2,500 m, monitored by heart rate ~170 bpm; thrice weekly) for 3 weeks. During this period, the HiHiLo group (n = 8) stayed in normobaric hypoxia (at ~2,800 m; 10 h.day-1), while the LoHi group (n = 8) resided near sea level. Before and immediately after the intervention, peak oxygen uptake and exercise-induced arterial hypoxemia responses (incremental cycle test) as well as running performance and time-domain heart rate variability (5-km time trial) were assessed. Hematological variables were monitored at baseline and on days 1, 7, 14 and 21 during the intervention. Results: Peak oxygen uptake and running performance did not differ before and after the intervention in either group (all P > 0.05). Exercise-induced arterial hypoxemia responses, measured both at submaximal (240 W) and maximal loads during the incremental test, and log-transformed root mean square of successive R-R intervals during the 4-min post-run recovery period, did not change (all P > 0.05). Hematocrit, mean reticulocyte absolute count and reticulocyte percentage increased above baseline levels on day 21 of the intervention (all P < 0.001), irrespective of group. Conclusions: Well-trained runners undertaking base training at moderate simulated altitude for 3 weeks, with or without hypoxic residence, showed no performance improvement, also with unchanged time-domain heart rate variability and exercise-induced arterial hypoxemia responses.

A pulmonary rehabilitation program is an effective strategy to improve forced vital capacity, muscle strength, and functional exercise capacity similarly in adults and older people with post-severe COVID-19 who required mechanical ventilation.

BACKGROUND: It is internationally known that our population is aging. At the same time, some patients with COVID-19, due to their symptoms, required mechanical ventilation (MV) and subsequent pulmonary rehabilitation (PR). This study aimed to compare the effects of a multimodal PR program "ADULT" versus "OLDER" people with COVID-19 who were on MV. METHODS: The intervention consisted of an 8-week hybrid PR program (2x week). Forced vital capacity (FVC) was measured at the beginning and end of PR, upper and lower limb strength was obtained through hand grip strength (HGS) and the sit-to-stand test (STST), respectively, and functional exercise capacity was measured with the 6-minute walking test (6MWT). RESULTS: The main results were an increase in the FVC in the ADULT and OLDER groups (time effect, P = 0.000; η2 = 0.27), an increase in HGS in the ADULT and OLDER groups (time effect, P = 0.000; η2 = 0.52), in the same way, the number of repetitions on the STST increased in the ADULT and OLDER groups (time effect, P = 0.000; η2 = 0.55). Finally, the distance covered on the 6MWT increased in the ADULT and OLDER groups (time effect, P = 0.000; η2 = 0.65). CONCLUSIONS: The PR program is an effective strategy to improve FVC, muscle strength, and functional exercise capacity similarly in adults and older people with post severe COVID-19 who required MV.

Effect of postoperative exercise training on physical function and quality of life of lung cancer patients with chronic obstructive pulmonary disease: A randomized controlled trial.

BACKGROUND: Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients. However, whether postoperative exercise is beneficial to lung cancer patients comorbid with chronic obstructive pulmonary disease remains unknown. METHODS: Eighty-four patients diagnosed with both lung cancer and chronic obstructive pulmonary disease were randomized into the exercise group and control group. Both groups were given standard postoperative rehabilitation for 1 week. After that, oxygen therapy (if needed) and nebulization were given to the control group, while patients in the exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the control group. The exercise programs consisted of 24 training sessions. RESULTS: In both groups, the functional status and the results of the pulmonary function test decreased from baseline to the endpoint. However, after surgery and the intervention program, both the maximal oxygen consumption in the cardiopulmonary exercise test and walking distance in the 6-minute walk test in the exercise group were significantly better than those in the control group [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = 0.016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = 0.040]. Force vital capacity and forced expiratory volume in the first second in the exercise group were better than those in the control group, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = 0.254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = 0.497]. The decline in the standard score of the QLQ-C30 (V3.0) was smaller in the exercise group, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = 0.318]. CONCLUSION: This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of chronic obstructive pulmonary disease.

Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.

BACKGROUND: Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. METHODS AND RESULTS: We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1. CONCLUSIONS: Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

Effect of home-based pulmonary rehabilitation on exercise capacity in post COVID-19 patients: a randomized controlled trail.

BACKGROUND: Coronavirus 2019 (COVID-19) is an epidemic condition that compromises various consequences. The goal of this study was to investigate the effect of home-based pulmonary rehabilitation on exercise capacity in patients with post COVID-19 syndrome. METHODS: The study was designed as a randomized control trial. A total of sixty-eight patients with post COVID-19 syndrome complaining of fatigue, dyspnea, and exercise intolerance participated in this study. Their ages ranged from 40 to 70 years old. The patients were randomly classified into two equal groups. The control group received usual medical care only, whereas the rehabilitation group received a selected home-based pulmonary rehabilitation exercise program plus the same usual medical care. The Physical Fitness Index (PFI), Chalder fatigue index, SF-36 questionnaire, dyspnea scale, and six-minute walk test (6 MWT) were measured before and after 12 weeks of intervention. RESULTS: The rehabilitation group showed a significant lower mean of Chalder fatigue (11.1 ± 0.94) and a higher mean of 6MWT (439.7 ± 25.3) and PFI (52.3 ± 10.2), in addition to a higher mean of the SF-36 Questionnaire (66.4 ± 3.7) and a significant improvement of dyspnea in the mMRC score (26.7%), grade 2, (63.3%), grade 1 (10%), and grade 0 with a p-value < 0.001 when compared to the control group. CONCLUSION: Home-based pulmonary rehabilitation (HBPR) for patients with post COVID-19 syndrome is effective and has a potential direct influence on exercise capacity, fatigue, dyspnea, and quality of life. HBPR could be considered an adjunctive, applicable, and low-cost therapy for patients with post COVID-19 syndrome. TRIAL REGISTRATION: The study was registered in Pan African Clinical Trial Registry as a clinical trial ID (PACTR202111640499636), November 2021.

Using reference equations to standardise incremental shuttle walk test performance in children and young people with chronic conditions and facilitate the evaluation of exercise capacity and disease severity.

AIMS: The aim was to evaluate whether standardised exercise performance during the incremental shuttle walk test (ISWT) can be used to assess disease severity in children and young people (CYP) with chronic conditions, through (1) identifying the most appropriate paediatric normative reference equation for the ISWT, (2) assessing how well CYP with haemophilia and cystic fibrosis (CF) perform against the values predicted by the best fit reference equation and (3) evaluating the association between standardised ISWT performance and disease severity. METHODS: A cross-sectional analysis was carried out using existing data from two independent studies (2018-2019) at paediatric hospitals in London,UK. CYP with haemophilia (n=35) and CF (n=134) aged 5-18 years were included. Published reference equations for standardising ISWT were evaluated through a comparison of populations, and Bland-Altman analysis was used to assess the level of agreement between distances predicted by each equation. Associations between ISWT and disease severity were assessed with linear regression. RESULTS: Three relevant reference equations were identified for the ISWT that standardised performance based on age, sex and body mass index (Vardhan, Lanza, Pinho). A systematic proportional bias of standardised ISWT was observed in all equations, most pronounced with Vardhan and Lanza; the male Pinho equation was identified as most appropriate. On average, CYP with CF and haemophilia performed worse than predicted by the Pihno equation, although the range was wide. Standardised ISWT, and not ISWT distance alone, was significantly associated with forced expiratory volume in 1 s in CYP with CF. Standardised ISWT in CYP with haemophilia was slightly associated with haemophilia joint health score, but this was not significant. CONCLUSIONS: ISWT performance may be useful in a clinic to identify those with worsening disease, but only when performance is standardised against a healthy reference population. The development of validated global reference equations is necessary for more robust assessment.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

BACKGROUND: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. METHODS: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. RESULTS: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. CONCLUSIONS: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.

Exercise Training Differentially Affects Skeletal Muscle Mitochondria in Rats with Inherited High or Low Exercise Capacity.

Exercise capacity has been related to morbidity and mortality. It consists of an inherited and an acquired part and is dependent on mitochondrial function. We assessed skeletal muscle mitochondrial function in rats with divergent inherited exercise capacity and analyzed the effect of exercise training. Female high (HCR)- and low (LCR)-capacity runners were trained with individually adapted high-intensity intervals or kept sedentary. Interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria from gastrocnemius muscle were isolated and functionally assessed (age: 15 weeks). Sedentary HCR presented with higher exercise capacity than LCR paralleled by higher citrate synthase activity and IFM respiratory capacity in skeletal muscle of HCR. Exercise training increased exercise capacity in both HCR and LCR, but this was more pronounced in LCR. In addition, exercise increased skeletal muscle mitochondrial mass more in LCR. Instead, maximal respiratory capacity was increased following exercise in HCRs' IFM only. The results suggest that differences in skeletal muscle mitochondrial subpopulations are mainly inherited. Exercise training resulted in different mitochondrial adaptations and in higher trainability of LCR. HCR primarily increased skeletal muscle mitochondrial quality while LCR increased mitochondrial quantity in response to exercise training, suggesting that inherited aerobic exercise capacity differentially affects the mitochondrial response to exercise training.

Association of Monocyte Count With Lung Function and Exercise Capacity Among Hospitalized COVID-19 Survivors: A 2-Year Cohort Study.

BACKGROUND: Abnormal changes of monocytes have been observed in acute COVID-19, whereas associations of monocyte count with long COVID were not sufficiently elucidated. METHODS: A cohort study was conducted among COVID-19 survivors discharged from hospital. The primary outcomes were core symptoms of long COVID, distance walked in 6 min, and lung function, and the secondary outcomes were health-related quality of life and healthcare use after discharge. Latent variable mixture modeling was used to classify individuals into groups with similar trajectory of monocyte count from discharge to 2-year after symptom onset. Multivariable adjusted generalized linear regression models and logistic regression models were used to estimate the associations of monocyte count trajectories and monocyte count at discharge with outcomes. RESULTS: In total, 1389 study participants were included in this study. Two monocyte count trajectories including high to normal high and normal trajectory were identified. After multivariable adjustment, participants in high to normal high trajectory group had an odds ratio (OR) of 2.52 (95% CI, 1.44-4.42) for smell disorder, 2.27 (1.27-4.04) for 6-min walking distance less than lower limit of normal range, 2.45 (1.08-5.57) for total lung capacity (TLC) < 80% of predicted, 3.37 (1.16-9.76) for personal care problem, and 1.70 (1.12-2.58) for rehospitalization after discharge at 2-year follow-up compared with those in normal trajectory group. Monocyte count at discharge showed similar results, which was associated with smell disorder, TLC < 80% of predicted, diffusion impairment, and rehospitalization. CONCLUSIONS: Monocyte count may serve as an easily accessible marker for long-term management of people recovering from COVID-19.

In adults with stable angina, PCI vs. a placebo procedure reduced angina symptoms at 12 wk.

SOURCE CITATION: Rajkumar CA, Foley MJ, Ahmed-Jushuf F, et al; ORBITA-2 Investigators. A placebo-controlled trial of percutaneous coronary intervention for stable angina. N Engl J Med. 2023;389:2319-2330. 38015442.

Effect of exercise training on heath, quality of life, exercise capacity in juvenile idiopathic arthritis: a meta-analysis of randomized controlled trials.

OBJECTIVE: Little is known about the efficacy and safety of exercise training on juvenile idiopathic arthritis (JIA). This study aims to investigate the effect of exercise on health, quality of life, and different exercise capacities in individuals with JIA. METHOD: A comprehensive search of Medline, Embase, Web of Science, and the Cochrane Library was conducted from database inception to October, 2023. Included studies were randomized controlled trials (RCTs) reporting the effects of exercise on JIA patients. Two independent reviewers assessed the literature quality using the Cochrane Collaboration's risk of bias tool. Standardized mean differences (SMD) were combined using random or fixed effects models. The level of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULT: Five RCTs met the inclusion criteria, containing 216 female participants and 90 males. The meta-analysis results showed that exercise had no significant effect on JIA patients based on the Child Health Assessment Questionnaire (CHAQ) (SMD=-0.32, 95%CI: -0.83, 0.19; I2 = 73.2%, P = 0.011) and Quality of Life (QoL) (SMD = 0.27, 95%CI: -0.04, 0.58; I2 = 29.4%, P = 0.243) and no significant effect on peak oxygen uptake (VO2peak). However, exercise significantly reduced visual analog scale (VAS) pain scores in JIA patients (SMD = 0.50, 95%CI: -0.90, -0.10; I2 = 50.2%, P = 0.134). The quality of evidence assessed by GRADE was moderate to very low. CONCLUSION: Exercise does not significantly affect the quality of life and exercise capacity in JIA patients but may relieve pain. More RCTs are needed in the future to explore the effects of exercise on JIA.

Effects of hypoxic compound exercise to promote HIF-1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila.

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.

A review regarding the article 'Supervised exercise training in heart failure with preserved ejection fraction: A systematic review and meta-analysis of randomized controlled trials'.

Heart failure is a clinical syndrome with different etiologies and phenotypes. For all forms, supervised exercise training and individual physical activity are class IA recommendations in current guidelines. Over the past two decades it has become recognized that physical deconditioning may play a key role in the progression of symptoms and poor outcomes. A number of prior studies have assessed the ability of exercise training to improve functional capacity in patients with HF. Most of these previous studies showed positive effects of exercise training on exercise capacity, quality of life, and biomarkers and observed relatively few complications during training. These studies also suggested that exercise training might improve survival and decrease HF hospitalizations. Despite the failure of pharmacological interventions to reduce mortality and hospitalization in HFpEF, exercise training has shown efficacy in improving maximal exercise capacity, assessed through peak oxygen consumption (peak V˙o2), in clinically stable patients. Nonetheless, there remains a safety concern regarding exercise training in HF. Although the complication rate for patients participating in cardiac rehabilitation has been reported to be extremely low, the complication rate for HF patients in clinical trials of exercise training has been substantially higher. One potential reason is the 100-fold increased risk for myocardial infarction and 50-fold increased risk of sudden death that exercisers, who are habitually sedentary, experience when initiating exercise training. Additionally, comprehensive insights into the potential effects of exercise training, not only on critical clinical outcomes such as hospitalization, mortality, and cardiovascular events but also on cost-effectiveness, require longer-term trials.

Improved pulmonary function and exercise tolerance despite persistent pulmonary fibrosis over 1 year after severe COVID-19 infection.

We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised. Overall, dyspnoea, cough and exhaustion did not improve and were not correlated with pulmonary function or radiographic fibrosis at 15 months, suggesting non-respiratory aetiologies. Monitoring persistent, and often subclinical, fibrotic interstitial abnormalities will be needed to determine their potential for future progression.