Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Mechanisms and consequences of excess exercise ventilation in fibrosing interstitial lung disease.

The causes and consequences of excess exercise ventilation (EEV) in patients with fibrosing interstitial lung disease (f-ILD) were explored. Twenty-eight adults with f-ILD and 13 controls performed an incremental cardiopulmonary exercise test. EEV was defined as ventilation-carbon dioxide output (⩒E-⩒CO2) slope ≥36 L/L. Patients showed lower pulmonary function and exercise capacity compared to controls. Lower DLCO was related to higher ⩒E-⩒CO2 slope in patients (P<0.05). 13/28 patients (46.4%) showed EEV, reporting higher dyspnea scores (P=0.033). Patients with EEV showed a higher dead space (VD)/tidal volume (VT) ratio while O2 saturation dropped to a greater extent during exercise compared to those without EEV. Higher breathing frequency and VT/inspiratory capacity ratio were observed during exercise in the former group (P<0.05). An exaggerated ventilatory response to exercise in patients with f-ILD is associated with a blunted decrease in the wasted ventilation in the physiological dead space and greater hypoxemia, prompting higher inspiratory constraints and breathlessness.

Dynamic Ventilatory Reserve During Incremental Exercise: Reference Values and Clinical Validation in Chronic Obstructive Pulmonary Disease.

Rationale: Ventilatory demand-capacity imbalance, as inferred based on a low ventilatory reserve, is currently assessed only at peak cardiopulmonary exercise testing (CPET). Peak ventilatory reserve, however, is poorly sensitive to the submaximal, dynamic mechanical ventilatory abnormalities that are key to dyspnea genesis and exercise intolerance. Objectives: After establishing sex- and age-corrected norms for dynamic ventilatory reserve at progressively higher work rates, we compared peak and dynamic ventilatory reserve for their ability to expose increased exertional dyspnea and poor exercise tolerance in mild to very severe chronic obstructive pulmonary disease (COPD). Methods: We analyzed resting functional and incremental CPET data from 275 controls (130 men, aged 19-85 yr) and 359 Global Initiative for Chronic Obstructive Lung Disease patients with stage 1-4 obstruction (203 men) who were prospectively recruited for previous ethically approved studies in three research centers. In addition to peak and dynamic ventilatory reserve (1 - [ventilation / estimated maximal voluntary ventilation] × 100), operating lung volumes and dyspnea scores (0-10 on the Borg scale) were obtained. Results: Dynamic ventilatory reserve was asymmetrically distributed in controls; thus, we calculated its centile distribution at every 20 W. The lower limit of normal (lower than the fifth centile) was consistently lower in women and older subjects. Peak and dynamic ventilatory reserve disagreed significantly in indicating an abnormally low test result in patients: whereas approximately 50% of those with a normal peak ventilatory reserve showed a reduced dynamic ventilatory reserve, the opposite was found in approximately 15% (P < 0.001). Irrespective of peak ventilatory reserve and COPD severity, patients who had a dynamic ventilatory reserve below the lower limit of normal at an isowork rate of 40 W had greater ventilatory requirements, prompting earlier attainment of critically low inspiratory reserve. Consequently, they reported higher dyspnea scores, showing poorer exercise tolerance compared with those with preserved dynamic ventilatory reserve. Conversely, patients with preserved dynamic ventilatory reserve but reduced peak ventilatory reserve reported the lowest dyspnea scores, showing the best exercise tolerance. Conclusions: Reduced submaximal dynamic ventilatory reserve, even in the setting of preserved peak ventilatory reserve, is a powerful predictor of exertional dyspnea and exercise intolerance in COPD. This new parameter of ventilatory demand-capacity mismatch may enhance the yield of clinical CPET in the investigation of activity-related breathlessness in individual patients with COPD and other prevalent cardiopulmonary diseases.

Cardiopulmonary exercise testing to indicate increased ventilatory variability in subjects with dysfunctional breathing.

BACKGROUND: Dysfunctional breathing (DB) is a common, but largely underappreciated, cause of chronic dyspnoea. Under visual inspection, most subjects with DB present with larger sequential changes in ventilation (V̇E) and breathing pattern (tidal volume (VT) and breathing frequency (f)) before and/or during incremental cardiopulmonary exercise testing (CPET). Currently, however, there are no objective criteria to indicate increased ventilatory variability in these subjects. METHODS: Twenty chronically dyspnoeic subjects with DB and 10 age- and sex-matched controls performed CPET on a cycle ergometer. Cut-offs to indicate increased V̇E, VT, f, and f/VT ratio variability (Δ = highest-lowest 20 s arithmetic mean) over the last resting minute (rest ), the 2sd min of unloaded exercise (unload ), and the 3rd min of loaded exercise (load ) were established by ROC curve analyses. RESULTS: Subjects with DB presented with increased V̇E, higher ventilatory variability, higher dyspnoea burden, and lower exercise capacity compared to controls (p < 0.05). ΔV̇Eload (>4.1 L/min), Δfrest (>5 breaths/min; bpm), Δfunload (>4 bpm), Δfload (>5 bpm), Δf/VTrest (>4.9 bpm/L), and Δf/VTload (>1.3 bpm/L) differentiated DB from a normal pattern (areas under the curve ranging from 0.729 to 0.845). High Δf, in particular, was associated with DB across all CPET phases. CONCLUSIONS: This study provides objective criteria to indicate increased ventilatory variability during incremental CPET in dyspnoeic subjects with DB. Large variability in breathing frequency seems particularly useful in this context, a finding that should be prospectively confirmed in larger studies.

Exertional oscillatory ventilation in subjects without heart failure reporting chronic dyspnoea.

Oscillatory ventilation detected on incremental cardiopulmonary exercise testing might be found in subjects without heart failure reporting exertional dyspnoea despite the best available therapy for their underlying cardiopulmonary disease https://bit.ly/3Tyl7bE.

Continuous Monitoring of Pulse Oximetry During the 6-Minute Walk Test Improves Clinical Outcomes Prediction in COPD.

BACKGROUND: Continuous monitoring of SpO2 throughout the 6-min walk test (6MWT) unveiled that some patients with respiratory diseases may present values across the test lower than SpO2 measured at the end of the test. Nevertheless, it remains unclear whether this approach improves the yield of walk-induced desaturation detection in predicting mortality and hospitalizations in patients with COPD. METHODS: Four hundred twenty-one subjects (51% males) with mild-very severe COPD underwent a 6MWT with continuous measurement of SpO2 . Exercise desaturation was defined as a fall in SpO2 ≥ 4%. All-cause mortality was assessed up to 6 y of follow-up and the rate of hospitalizations in the year succeeding the 6MWT. RESULTS: One hundred forty-nine subjects (35.4%) died during a mean (interquartile) follow-up of 55.5 (30.2-64.1) months. Desaturation was observed in 299/421 (71.0%). SpO2 along the test was < end SpO2 (88 [82-92]% vs 90 [84-93]%, P < .001). Desaturation detected only during (but not at the end of) the test was found in 81/421 (19.2%) participants. Multivariate Cox regression model adjusted for sex, body composition, FEV1, residual volume/total lung capacity ratio, walk distance, O2 supplementation during the test, and comorbidities retained the presence of desaturation either at the end (1.85 [95% CI 1.02-3.36]) or only along the test (2.08 [95% CI 1.09-4.01]) as significant predictors of mortality. The rate of hospitalizations was higher in those presenting with any kind of desaturation compared to those without exercise desaturation. Logistic regression analysis revealed that walking interruption and diffusing capacity of the lung for carbon monoxide predicted desaturation observed only during the test. CONCLUSIONS: O2 desaturation missed by end-exercise SpO2 but exposed by measurements during the test was independently associated with all-cause mortality and hospitalizations in subjects with COPD.

Exertional ventilation/carbon dioxide output relationship in COPD: from physiological mechanisms to clinical applications.

There is well established evidence that the minute ventilation (V'E)/carbon dioxide output (V'CO2 ) relationship is relevant to a number of patient-related outcomes in COPD. In most circumstances, an increased V'E/V'CO2 reflects an enlarged physiological dead space ("wasted" ventilation), although alveolar hyperventilation (largely due to increased chemosensitivity) may play an adjunct role, particularly in patients with coexistent cardiovascular disease. The V'E/V'CO2 nadir, in particular, has been found to be an important predictor of dyspnoea and poor exercise tolerance, even in patients with largely preserved forced expiratory volume in 1 s. As the disease progresses, a high nadir might help to unravel the cause of disproportionate breathlessness. When analysed in association with measurements of dynamic inspiratory constraints, a high V'E/V'CO2 is valuable to ascertain a role for the "lungs" in limiting dyspnoeic patients. Regardless of disease severity, cardiocirculatory (heart failure and pulmonary hypertension) and respiratory (lung fibrosis) comorbidities can further increase V'E/V'CO2 A high V'E/V'CO2 is a predictor of poor outcome in lung resection surgery, adding value to resting lung hyperinflation in predicting all-cause and respiratory mortality across the spectrum of disease severity. Considering its potential usefulness, the V'E/V'CO2 should be valued in the clinical management of patients with COPD.

Sleep quality and architecture in COPD: the relationship with lung function abnormalities.

OBJECTIVE: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. METHODS: We retrospectively assessed data from COPD 181 patients ≥ 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. RESULTS: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (ß = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (ß = -0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (ß = 0.085; R2 = 15%; p = 0.001). CONCLUSIONS: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

Proportional Assist Ventilation Improves Leg Muscle Reoxygenation After Exercise in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Respiratory muscle unloading through proportional assist ventilation (PAV) may enhance leg oxygen delivery, thereby speeding off-exercise oxygen uptake ( V . ⁢ O 2 ) kinetics in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). METHODS: Ten male patients (HFrEF = 26 ± 9%, age 50 ± 13 years, and body mass index 25 ± 3 kg m2) underwent two constant work rate tests at 80% peak of maximal cardiopulmonary exercise test to tolerance under PAV and sham ventilation. Post-exercise kinetics of V . ⁢ O 2 , vastus lateralis deoxyhemoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy, and cardiac output (Q T ) by impedance cardiography were assessed. RESULTS: PAV prolonged exercise tolerance compared with sham (587 ± 390 s vs. 444 ± 296 s, respectively; p = 0.01). PAV significantly accelerated V . ⁢ O 2 recovery (τ = 56 ± 22 s vs. 77 ± 42 s; p < 0.05), being associated with a faster decline in Δ[deoxy-Hb + Mb] and Q T compared with sham (τ = 31 ± 19 s vs. 42 ± 22 s and 39 ± 22 s vs. 78 ± 46 s, p < 0.05). Faster off-exercise decrease in Q T with PAV was related to longer exercise duration (r = -0.76; p < 0.05). CONCLUSION: PAV accelerates the recovery of central hemodynamics and muscle oxygenation in HFrEF. These beneficial effects might prove useful to improve the tolerance to repeated exercise during cardiac rehabilitation.

Factors influencing self-selected walking speed in fibrotic interstitial lung disease.

This study aimed to investigate the walking economy and possible factors influencing self-selected walking speed (SSWS) in patients with fibrotic interstitial lung disease (ILD) compared to controls. In this study, 10 patients with ILD (mean age: 63.8 ± 9.2 years, forced expiratory volume in the first second: 56 ± 7% of predicted) and 10 healthy controls underwent resting pulmonary function tests, cardiopulmonary exercise, and submaximal treadmill walking tests at different speeds. The walking economy was assessed by calculating the cost-of-transport (CoT). Dynamic stability was assessed by stride-to-stride fluctuations using video recordings. Patients with ILD showed reduced peak oxygen uptake with a tachypneic breathing pattern and significant oxygen desaturation during exercise. The CoT did not differ between the groups (p = 0.680), but dyspnea and SpO2 were higher and lower, respectively, in patients with ILD at the same relative speeds. SSWS was reduced in ILD patients (2.6 ± 0.9 vs. 4.2 ± 0.4 km h-1 p = 0.001) and did not correspond to the energetically optimal walking speed. Dynamic stability was significantly lower in patients with ILD than in healthy controls, mainly at lower speeds. Patients with ILD presented a similar cost of transport compared to healthy controls; however, they chose lower SSWS despite higher walking energy expenditure. Although walking stability and dyspnea were negatively affected, these factors were not associated with the slower walking speed chosen by individuals with ILD.

Clinical Interpretation of Cardiopulmonary Exercise Testing: Current Pitfalls and Limitations.

Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O2) despite a low peak WR. Among the determinants of V̇O2, only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O2 delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that "the lungs" are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased "wasted" ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO2 might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician.

Responses to progressive exercise in subjects with chronic dyspnea and inspiratory muscle weakness.

INTRODUCTION: Inspiratory muscle weakness (IMW) is a potential cause of exertional dyspnea frequently under-appreciated in clinical practice. Cardiopulmonary exercise testing (CPET) is usually requested as part of the work-up for unexplained breathlessness, but the specific pattern of exercise responses ascribed to IMW is insufficiently characterized. OBJECTIVES: To identify the physiological and sensorial responses to progressive exercise in dyspneic patients with IMW without concomitant cardiorespiratory or neuromuscular diseases. METHODS: Twenty-three subjects (18 females, 55.2 ± 16.9 years) complaining of chronic daily life dyspnea (mMRC = 3 [2-3]) plus maximal inspiratory pressure < the lower limit of normal and 12 matched controls performed incremental cycling CPET. FEV1/FVC<0.7, significant abnormalities in chest CT or echocardiography, and/or an established diagnosis of neuromuscular disease were among the exclusion criteria. RESULTS AND CONCLUSION: Patients presented with reduced aerobic capacity (peak V̇O2: 79 ± 26 vs 116 ± 21 %predicted), a tachypneic breathing pattern (peak breathing frequency/tidal volume = 38.4 ± 22.7 vs 21.7 ± 14.2 breaths/min/L) and exercise-induced inspiratory capacity reduction (-0.17 ± 0.33 vs 0.10 ± 0.30 L) (all P < .05) compared to controls. In addition, higher ventilatory response (ΔV̇E/ΔV̇CO2 = 34.1 ± 6.7 vs 27.0 ± 2.3 L/L) and symptomatic burden (dyspnea and leg discomfort) to the imposed workload were observed in patients. Of note, pulse oximetry was similar between groups. Reduced aerobic capacity in the context of a tachypneic breathing pattern, inspiratory capacity reduction and preserved oxygen exchange during progressive exercise should raise the suspicion of inspiratory muscle weakness in subjects with otherwise unexplained breathlessness.

Sleep quality and architecture in COPD: the relationship with lung function abnormalities / Qualidade e arquitetura do sono na DPOC: relação com anormalidades da função pulmonar

ABSTRACT Objective: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. Methods: We retrospectively assessed data from COPD 181 patients ≥ 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. Results: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (β = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (β = −0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (β = 0.085; R2 = 15%; p = 0.001). Conclusions: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

RESUMO Objetivo: O comprometimento da mecânica respiratória e das trocas gasosas pode contribuir para distúrbios do sono em pacientes com DPOC. Objetivamos avaliar associações putativas de diferentes domínios da função pulmonar (limitação do fluxo aéreo, volumes pulmonares e eficiência das trocas gasosas) com parâmetros da qualidade e arquitetura do sono na DPOC derivados da polissonografia (PSG). Métodos: Avaliamos retrospectivamente dados de 181 pacientes com DPOC e idade ≥ 40 anos que foram submetidos a espirometria, pletismografia e PSG de noite inteira. Modelos de regressão linear univariada e multivariada foram utilizados para avaliar a associação de variáveis de função pulmonar com a eficiência do sono (tempo total de sono/tempo total de registro) e outros parâmetros derivados da PSG que refletem a qualidade do sono. Resultados: A gravidade da DPOC foi bem distribuída na amostra (VEF1 pós-broncodilatador variando de 25% a 128% do previsto): DPOC leve (40,3%), DPOC moderada (43,1%) e DPOC grave-muito grave (16,6%). A PSG revelou uma alta frequência de apneia obstrutiva do sono (64,1%) e dessaturação noturna significativa (nadir médio da oximetria de pulso = 82,2% ± 6,9%). Após controle para idade, sexo, IMC, índice de apneia-hipopneia, dessaturação noturna, comorbidades e prescrição de psicotrópicos, a relação VEF1/CVF apresentou associação com a eficiência do sono (β = 25,366; R2 = 14%; p < 0,001), enquanto a DLCO previu a latência para o início do sono (β = −0,314; R2 = 13%; p < 0,001) e o tempo de sono rapid eye movement/tempo total de sono em % (β = 0,085; R2 = 15%; p = 0,001). Conclusões: As variáveis de função pulmonar que refletem a gravidade do comprometimento do fluxo aéreo e das trocas gasosas, ajustadas para alguns potenciais fatores de confusão, apresentaram fraca relação com os resultados da PSG nos pacientes com DPOC. A contribuição direta das características fisiopatológicas da DPOC para os parâmetros da qualidade do sono medidos objetivamente parece ser menos importante do que se supunha anteriormente.

Impacts of post-radiotherapy lymphocyte count on progression-free and overall survival in patients with stage III lung cancer.

BACKGROUND: We evaluated the impact of thoracic radiation in patients with non-small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of chemotherapy, and radiation doses in healthy lung tissue. METHODS: Patients with stage III NSCLC, ECOG 0 to 2, receiving radiotherapy with or without chemotherapy were prospectively evaluated. All patients should be treated with three-dimensional radiotherapy and received biologically effective doses (BED10α/ß 10) of 48 to 80 Gy. Peripheral blood lymphocyte total counts were measured at the start of radiotherapy and at 2, 6 and 12 months after radiotherapy. Along with lymphocytes, PTV and doses of 5 Gy and 20 Gy in healthy lung tissue were also evaluated as potential factors influencing overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 46 patients were prospectively evaluated from April 2016 to August 2019, with a median follow-up of 13 months (interquartile range, 1-39 months). The median of OS of all cohort was 22,8 months (IC 95% 17,6-28,1) and the median PFS was 19,5 months (IC 95%: 14,7-24,2). Most patients received concurrent or neoadjuvant chemotherapy (43; 93.4%). No patient received adjuvant immunotherapy. The lower the lymphocyte loss at 6 months after radiotherapy (every 100 lymphocytes/mcL), the greater the chance of PFS (HR, 0.44; 95%CI, 0.25-0.77; P = 0.004) and OS (HR, 0.83; 95%CI, 0.70-0.98; P = 0.025; P = 0.025). BED was a protective factor for both PFS (HR, 0.52; 95%CI 0.33-0.83; P = 0.0006) and OS (HR, 0.73; 95%CI 0.54-0.97; P = 0.029). CONCLUSIONS: Our results suggest that lymphocyte depletion after radiotherapy reduces tumor control and survival in patients with stage III lung cancer. Radiation doses equal or higher than 60 Gy (BED10 72 Gy) improve PFS and OS, but they negatively affect lymphocyte counts for months, which reduces survival and the potential of immunotherapy. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Thoracic irradiation for locally advanced lung cancer depletes T lymphocytes for months. Patients whose lymphocyte loss is lower have better overall survival and progression-free survival. WHAT THIS STUDY ADDS: It is necessary to protect the lymphocyte population, as well as other organs at risk. New forms of irradiation for large fields are needed. Furthermore, could immunotherapy before chemo-radiotherapy, with a greater number of lymphocytes, bring an even better result?

Are the "critical" inspiratory constraints actually decisive to limit exercise tolerance in COPD?

The concept of critical inspiratory constraints is key to the modern understanding of exercise pathophysiology in patients with moderate-to-severe COPD https://bit.ly/2A6bCxD.

The Lung Function Laboratory to Assist Clinical Decision-making in Pulmonology: Evolving Challenges to an Old Issue.

The lung function laboratory frequently provides relevant information to the practice of pulmonology. Clinical interpretation of pulmonary function and exercise tests, however, has been complicated more recently by temporal changes in demographic characteristics (higher life expectancy), anthropometric attributes (increased obesity prevalence), and the surge of polypharmacy in a sedentary population with multiple chronic degenerative diseases. In this narrative review, we concisely discuss some key challenges to test interpretation that have been affected by these epidemiologic shifts: (a) the confounding effects of advanced age and severe obesity, (b) the contemporary controversies in the diagnosis of obstruction (including asthma and/or COPD), (c) the importance of considering the diffusing capacity of the lung for carbon monoxide (Dlco)/"accessible" alveolar volume (carbon monoxide transfer coefficient) in association with Dlco to uncover the causes of impaired gas exchange, and (d) the modern role of the pulmonary function laboratory (including cardiopulmonary exercise testing) in the investigation of undetermined dyspnea. Following a Bayesian perspective, we suggest interpretative algorithms that consider the pretest probability of abnormalities as indicated by additional clinical information. We, therefore, adopt a pragmatic approach to help the practicing pulmonologist to apply the information provided by the lung function laboratory to the care of individual patients.

A frame of reference for assessing the intensity of exertional dyspnoea during incremental cycle ergometry.

Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation (V' E). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort.Reference ranges based on dyspnoea percentiles (0-10 Borg scale) at standardised work rates and V' E were established in 275 apparently healthy subjects aged 20-85 years (131 men). They were compared with values recorded in a randomly selected "validation" sample (n=451; 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea ("testing sample") who terminated CPET due to leg discomfort (86 men).Iso-work rate and, to a lesser extent, iso-V' E reference ranges (5th-25th, 25th-50th, 50-75th and 75th-95th percentiles) increased as a function of age, being systematically higher in women (p<0.01). There were no significant differences in percentiles distribution between "reference" and "validation" samples (p>0.05). Submaximal dyspnoea-work rate scores fell within the 75th-95th or >95th percentiles in 108 out of 118 (91.5%) subjects of the "testing" sample who showed physiological abnormalities known to elicit exertional dyspnoea, i.e. ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically fell in the 5th-50th range in subjects without those abnormalities (p<0.001).This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labelled as "non-dyspnoeic" while providing mechanistic insights into the genesis of this distressing symptom.