Self-reported dyspnoea and shortness of breathing deterioration in long-term survivors after segmentectomy or lobectomy for early-stage lung cancer.

OBJECTIVES: The aim of this study was to assess the self-reported current dyspnoea and perioperative changes of dyspnoea in long-term survivors after minimally invasive segmentectomy or lobectomy for early-stage lung cancer. METHODS: Cross-sectional telephonic survey of patients alive and disease-free as of March 2023, with pathologic stage IA1-2, non-small-cell lung cancer, assessed 1-5 years after minimally invasive segmentectomy or lobectomy (performed from January 2018 to January 2022). Current dyspnoea level: Baseline Dyspnoea Index score <10. Perioperative changes of dyspnoea were assessed using the Transition Dyspnoea Index. A negative Transition Dyspnoea Index focal score indicates perioperative deterioration in dyspnoea. Mixed effect models were used to examine demographic, medical and health-related correlates of current dyspnoea and changes in dyspnoea level. RESULTS: A total of 152 of 236 eligible patients consented or were available to respond to the telephonic interview(67% response rate): 90 lobectomies and 62 segmentectomies. The Baseline Dyspnoea Index score was lower (greater dyspnoea) in lobectomy patients (median 7, interquartile range 6-10) compared to segmentectomy (median 9, interquartile range 6-11), P = 0.034. 70% of lobectomy patients declared to have a current dyspnoea vs 53% after segmentectomy, P = 0.035. 82% of patients after lobectomy reported a perioperative deterioration in their dyspnoea compared to 57% after segmentectomy, P = 0.002. Mixed effect logistic regression analysis adjusting for patient-related factors and time elapsed from operation showed that segmentectomy was associated with a reduced risk of perioperative dyspnoea deterioration (as opposed to lobectomy) (Odds ratio (OR) 0.31, P = 0.004). CONCLUSIONS: Our findings may be valuable to inform the shared decision-making process by complementing objective data on perioperative changes of pulmonary function.

Impact of lung cancer screening on surgical stage distribution and surgical practice: a regional analysis of patients operated in and out of a screening program.

OBJECTIVES: The aim of this study was to assess variations in surgical stage distribution in 2 centres within the same UK region. One centre was covered by an active screening program started in November 2018 and the other was not covered by screening. METHODS: Retrospective analysis of 1895 patients undergoing lung resections (2018-2022) in 2 centres. Temporal distribution was tested using Chi-squared for trends. A lowess curve was used to plot the proportion of stage 1A patients amongst those operated over the years. RESULTS: The surgical populations in the 2 centres were similar. In the screening unit (SU), we observed a 18% increase in the proportion of patients with clinical stage IA in the recent phase compared to the early phase (59% vs 50%, P = 0.004), whilst this increase was not seen in the unit without screening. This difference was attributable to an increase of cT1aN0 patients in the SU (16% vs 11%, P = 0.035) which was not observed in the other unit (10% vs 8.2%, P = 0.41). In the SU, there was also a three-fold increase in the proportion of sublobar resections performed in the recent phase compared to the early one (35% vs 12%, P < 0.001). This finding was not evident in the unit without screening. CONCLUSIONS: Lung cancer screening is associated with a higher proportion of lung cancers being detected at an earlier stage with a consequent increased practice of sublobar resections.

Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection.

OBJECTIVES: Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections. METHODS: Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014-August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality. RESULTS: A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality. CONCLUSIONS: VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.

Minimally invasive segmentectomy and lobectomy for peripheral stage IA1-2 non-small-cell lung cancer: a case-matched cohort study from a UK Centre.

OBJECTIVES: The objective of this study is to compare in a real-world series the short- and long-term results of segmentectomy and lobectomy for peripheral clinical stage IA non-small-cell lung cancer (NSCLC). METHODS: Single-centre cohort study including a series of consecutive patients undergoing minimally invasive segmentectomy or lobectomy for peripheral (outer third of the lung) clinical stage IA NSCLC (January 2017-August 2022). Propensity score case matching analysis generated 2 matched groups of patients undergoing segmentectomy or lobectomy. Short-term (morbidity and mortality) and long-term [overall survival and event-free survival (EFS)] outcomes were compared between the 2 matched groups. EFS was calculated by including death resulting from any cause and any recurrence as events. RESULTS: Propensity score generated 118 pairs of patients undergoing minimally invasive segmentectomy or lobectomy. The median follow-up was 30 months (95% confidence limits (CL) 4-64). The median postoperative length of stay was 4 days in both groups. Ninety-day mortality was similar (segmentectomy 2.5% versus lobectomy 1.7%, P = 1). Three-year overall survival [segmentectomy 87% (76-93) versus lobectomy 81% (72-88), P = 0.73] and EFS [segmentectomy 82% (72-90) versus lobectomy 78% (68-84), P = 0.52] did not differ between the groups. Loco-regional recurrence rate [segmentectomy 4.2% (5/118) versus lobectomy 9.3% (11/118), P = 0.19] was similar despite a lower nodal upstaging [segmentectomy 3.4% (4/118) versus lobectomy 14% (17/118), P = 0.005]. The occurrence of compromised resection margins (pR1 or pR uncertain) was similar between the groups [segmentectomy 7.6% (9/118) versus lobectomy 9.3% (11/118), P = 0.81]. CONCLUSIONS: This observational series confirms the non-inferiority of segmentectomy compared to lobectomy in treating peripherally located stage IA NSCLC.

Prolonged air leak after segmentectomy: incidence and risk factors.

Background: We designed this study to investigate the rate and risk factors of prolonged air leak (PAL) in patients undergoing pulmonary segmentectomy in our unit. Methods: We performed a retrospective cohort study on 191 patients undergoing pulmonary segmentectomy (January 2017-August 2021). A PAL was defined as an air leak >5 days. Results: One hundred and sixty-eight segmentectomies were performed using video-assisted thoracoscopic surgery (VATS), 13 were open operations and 10 were robotic. PAL occurred in 36 patients (19%). Their average post-operative stay was 2.4 days longer than those without PAL. Logistic regression analysis showed that a low preoperative carbon monoxide lung diffusion capacity (DLCO) (OR 0.98, P<0.001), low body mass index (BMI) (OR 0.95, P=0.002) and the performance of complex segmentectomies (OR 2.2, P<0.001). were significantly associated with PAL. Conclusions: Pulmonary segmentectomies are associated with a not negligible risk of PAL when using real world data, especially in patients with compromised pulmonary function and after complex segmentectomies. This finding is useful to inform the decision-making process.

Video-Assisted-Thoracoscopic-Surgery Pleural Decorticator for Emergency Empyema Surgery.

BACKGROUND/NEED: Pleural empyemas carry a high morbidity and mortality. Some can be managed with medical treatment but most require some form of surgery with the goals to remove the infected material from the pleural space and to help re-expand the collapsed lung. Keyhole surgery by Video Assisted Thoracoscopy Surgery (VATS) is rapidly becoming a common approach to deal with early stage empyemas to avoid larger, more painful thoracotomies that hinder recovery. However, the ability to achieve those aforementioned goals is often hindered by VATS surgery due to the instruments available. METHODOLOGY AND DEVICE DESCRIPTION: We have developed a simple instrument called the "VATS Pleural Debrider" to achieve those goals in empyema surgery that can be used in keyhole surgery. PRELIMINARY RESULTS: We have used this device in over 90 patients with no peri-operative mortality and a low re-operation rate. CURRENT STATUS: Used in routine urgent/emergency pleural empyema surgery across 2 cardiothoracic surgery centres.

A risk model to predict an unplanned admission to the intensive care unit following lung resection.

OBJECTIVES: The goal of this study was to develop a risk-adjusting model to stratify the risk of an unplanned admission to the intensive care unit (following lung resection). METHODS: We performed a retrospective analysis of 3123 patients undergoing anatomical lung resections (2014-2019) in 2 centres. A risk score was developed by testing several variables for a possible association with a subsequent ICU admission using stepwise logistic regression analyses, validated by the bootstrap resampling technique. Variables associated with ICU admission were assigned weighted scores based on their regression coefficients. These scores were summed for each patient to generate the ICU risk score, and patients were grouped into risk classes. RESULTS: A total of 103 patients (3.3%) required an unplanned admission to the ICU after the operation. The average ICU stay was 17.6 days. The following variables remained significantly associated with ICU admission following logistic regression: male gender (P = 0.004), body mass index <18.5 (P = 0.002), predicted postoperative forced expiratory volume in 1 s < 60% (P = 0.004), predicted postoperative carbon monoxide lung diffusion capacity <50% (P = 0.013), open access (P = 0.004) and pneumonectomy (P = 0.041). All variables were weighted 1 point except body mass index <18.5 (2 points). The final ICU risk score ranged from 0 to 7 points. Patients were grouped into 6 risk classes showing an incremental unplanned ICU admission rate: class A (score 0), 0.7%; class B (score 1), 1.7%; class C (score 2), 3%; class D (score 3), 7.1%; class E (score 4), 12%; and class F (score > 4), 13% (P < 0.001). CONCLUSIONS: This risk score may assist in reliably planning the response to a sudden increase in the demand of critical care resources.

Impact of the type of initial intervention on the outcomes of lung volume reduction for emphysema: a propensity matched study.

Background: The type of initial intervention i.e., endobronchial valve (EBV) implantation or lung volume reduction surgery (LVRS) to be offered as initial intervention remains vague in the treatment of emphysema-chronic obstructive pulmonary disease (COPD) patients. Aim of the present study was to compare the outcomes of EBV with that of LVRS in emphysema patients who could have both offered as an initial intervention. Methods: The outcomes of 44 EBV patients were retrospectively compared to the outcomes of 44 matched LVRS patients (matched for age, gender, performance status, body mass index (BMI), lung functions, comorbidities and exercise tolerance, matching tolerance 0.2) treated in a single institute within a 5-year period. The median follow-up was 32 months (maximum duration 84 months). Results: Mean age was 61.91±9.48 years and 55 (62.5%) were male. Postoperative morbidity was similar but length of stay (LOS) was longer in the LVRS group (median 10 vs. 6 days, P=0.006). Re-interventions were more frequent in the EBV versus LVRS group (52.3% vs. 20.5%, P=0.002) and so was the overall number of re-interventions (median 2 vs. 1, P<0.01). Breathing improved in more LVRS patients (86.4% vs. 70.5%, P<0.002). The decrease of the COPD Assessment Test (CAT) score was less significant in the EBV group (P=0.034). Survival was similar between 2 groups (P=0.350). Conclusions: EBV or LVRS as initial intervention are similar in terms of morbidity and mortality. EBV showed shorter LOS whilst LVRS necessitated less but more severe re-interventions and led to better overall quality of life.

Eurolung risk score is associated with long-term survival after curative resection for lung cancer.

OBJECTIVE: The study objective was to verify whether the Eurolung score was associated with long-term prognosis after lung cancer resection. METHODS: A total of 1359 consecutive patients undergoing anatomic lung resection (1136 lobectomies, 103 pneumonectomies, 120 segmentectomies) (2014-2018) were analyzed. The parsimonious aggregate Eurolung2 score was calculated for each patient. Median follow-up was 802 days. Survival distribution was estimated by the Kaplan-Meier method. Cox proportional hazard regression and competing risk regression analyses were used to assess the independent association of Eurolung with overall and disease-specific survival. RESULTS: Patients were grouped into 4 classes according to their Eurolung scores (A 0-2.5, B 3-5, C 5.5-6.5, D 7-11.5). Most patients were in class A (52%) and B (33%), 8% were in class C, and 7% were in class D. Five-year overall survival decreased across the categories (A: 75%; B: 52%; C: 29%; D: 27%, log rank P < .0001). The score stratified the 3-year overall survival in patients with pT1 (P < .0001) or pT>1 (P < .0001). In addition, the different classes were associated with incremental risk of long-term overall mortality in patients with pN0 (P < .0001) and positive nodes (P = .0005). Cox proportional hazard regression and competing regression analyses showed that Eurolung aggregate score remained significantly associated with overall (hazard ratio, 1.19; P < .0001) and disease-specific survival after adjusting for pT and pN stage (hazard ratio, 1.09; P = .005). CONCLUSIONS: Eurolung aggregate score was associated with long-term survival after curative resection for cancer. This information may be valuable to inform the shared decision-making process and the multidisciplinary team discussion assisting in the selection of the most appropriate curative treatment in high-risk patients.

Poor preoperative quality of life predicts prolonged hospital stay after VATS lobectomy for lung cancer.

OBJECTIVES: The aim of this study was to assess whether quality of life (QoL) scales are associated with postoperative length of stay (LoS) following video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer. METHODS: This is a single-centre retrospective analysis on 250 consecutive patients submitted to VATS lobectomies (233) or segmentectomies (17) over a period of 3 years. QoL was assessed in all patients by the self-administration of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 questionnaire. The individual QoL scales were tested for possible association with LoS along with other objective baseline and surgical parameters using univariable and multivariable analyses. RESULTS: Thirty-day cardiopulmonary and mortality rates were 22% and 2.4%. The median LoS was 4 days [interquartile range (IQR) 3-7]. Fifty-one (20%) patients remained in hospital longer than 7 days after surgery (upper quartile). General health [global health score (GHS)] (P = 0.019), physical function (P = 0.014) and role functioning (P = 0.016) scales were significantly worse in patients with prolonged stay. They were highly correlated between each other and tested separately in different logistic regression analyses. The best model resulted the one containing GHS (P = 0.032) along with age, low force expiratory volume in 1 s and carbon monoxide lung diffusion capacity and history of cerebrovascular disease. Fifty-nine patients had GHS <58 (lower interquartile value). Thirty-one percent of them experienced prolonged hospital stay (vs 17% of those with higher GHS, P = 0.027). CONCLUSIONS: Preoperative patient-reported QoL was associated with prolonged postoperative hospital stay. Baseline QoL status should be taken into consideration to implement psychosocial supportive programmes in the context of enhanced recovery after surgery.

Correction to: Long-Term Outcomes in Percutaneous Radiofrequency Ablation for Histologically Proven Colorectal Lung Metastasis.

In the introduction section on line 7, the following sentence "A large epidemiological study of colorectal cancer patients with lung metastases found 3 and 5-year survival rates of 1.3% and 6.9%" should actually be "A large epidemiological study of colorectal cancer patients with lung metastases found 3 and 5-year survival rates of 11.3% and 6.9%".

Ninety-day hospital costs associated with prolonged air leak following lung resection.

OBJECTIVES: Our goal was to assess the postoperative 90-day hospital costs of patients with prolonged air leak (PAL) including costs incurred after discharge from the initial index hospitalization. METHODS: We performed a retrospective analysis of 982 patients undergoing lobectomy (898) or segmentectomy (78) (April 2014-August 2018). A total of 167 operations were open, 780 were video-assisted thoracoscopic surgery and 28 were robotic. A PAL was defined as an air leak >5 days. The 90-day postoperative costs included all fixed and variable costs incurred during the 90 days following surgery. The postoperative costs of patients with and without PAL were compared. The independent association of PAL with postoperative 90-day costs was tested after adjustment for patient-related factors and other complications by a multivariable regression analysis. RESULTS: PAL occurred in 261 patients (27%). Their postoperative stay was 4 days longer than that of those without PAL (9.6 vs 5.7; P < 0.0001). Compared to patients without PAL, those with PAL had 27% higher index postoperative costs [7354€, standard deviation (SD) 7646 vs 5759€, SD 7183, P < 0.0001] and 40% higher 90-day postoperative costs (18 340€, SD 23 312 vs 13 102€, SD 10 264; P < 0.0001). The relative postoperative costs (the difference between 90-day and index postoperative costs) were 50% higher in PAL patients compared to non-PAL patients (P < 0.0001) and accounted for 60% of the total 90-day costs. Multivariable regression analysis showed that PAL remained an independent factor associated with 90-day costs (P < 0.0001) along with the occurrence of other cardiopulmonary complications (P < 0.0001), male gender (P = 0.018), low carbon monoxide lung diffusion capacity (P = 0.043) and thoracotomy approach (P = 0.022). CONCLUSIONS: PAL is associated not only with increased index hospitalization costs but also with increased costs after discharge. Evaluation of the cost-effectiveness of measures to prevent air leaks should also include post-discharge costs.

Exploratory cost-effectiveness model of electromagnetic navigation bronchoscopy (ENB) compared with CT-guided biopsy (TTNA) for diagnosis of malignant indeterminate peripheral pulmonary nodules.

INTRODUCTION: Lung cancer is accountable for 35 000 deaths annually, and prognosis is improved when the cancer is diagnosed early. CT-guided biopsy (transthoracic needle aspiration, TTNA) and electromagnetic navigation bronchoscopy (ENB) can be used to investigate indeterminate pulmonary nodules if the patient is unfit for surgery. However, there is a paucity of clinical and health economic evidence that directly compares ENB with TTNA in this population group. This cost-effectiveness study aimed to explore potential scenarios whereby ENB may be considered cost-effective when compared with TTNA. METHODS: A cohort decision analytic model was developed using a UK National Health Service perspective. ENB was assumed to have equal sensitivity to TTNA at 82%. Lifetime costs and quality-adjusted life-year (QALY) gain were calculated to estimate the net monetary benefit at a £20 000 per QALY threshold. Sensitivity analyses were used to explore scenarios where ENB could be considered a cost-effective intervention. RESULTS: Under the assumption that ENB has equal efficacy to TTNA, ENB was found to be dominant (less costly and more effective) when compared with TTNA, due to having a reduced risk and cost of adverse events. This conclusion was most sensitive to changes in the cost of intervention, estimates of effectiveness and adverse event rates. DISCUSSION: ENB is expected to be cost-effective when the likelihood of an accurate diagnosis is equal to (or better than) TTNA, which may occur in certain subgroups of patients in whom TTNA is unlikely to accurately diagnose malignancy or when an experienced practitioner achieves a high accuracy with ENB.

Long-Term Outcomes in Percutaneous Radiofrequency Ablation for Histologically Proven Colorectal Lung Metastasis.

INTRODUCTION: To evaluate the long-term outcome of image-guided radiofrequency ablation (RFA) when treating histologically confirmed colorectal lung metastasis in terms of overall survival (OS), progression-free survival (PFS) and local tumour control (LTC). MATERIALS AND METHODS: Retrospective single-centre study. Consecutive RFA treatments of histologically proven lung colorectal metastases between 01/01/2008 and 31/12/14. The primary outcome was patient survival (OS and PFS). Secondary outcomes were local tumour progression (LTP) and complications. Prognostic factors associated with OS/ PFS were determined by univariate and multivariate analyses. RESULTS: Sixty patients (39 males: 21 females; median age 69 years) and 125 colorectal lung metastases were treated. Eighty percent (n = 48) also underwent lung surgery for lung metastases. Mean metastasis size (cm) was 1.4 ± 0.6 (range 0.3-4.0). Median number of RFA sessions was 1 (1-4). During follow-up (median 45.5 months), 45 patients died (75%). The estimated OS and PFS survival rates at 1, 3, 5, 7, 9 years were 96.7%, 74.7%, 44.1%, 27.5%, 16.3% (median OS, 52 months) and 66.7%, 31.2%, 25.9%, 21.2% and 5.9% (median PFS, 19 months). The LTC rate was 90% with 6 patients developing LTP with 1-, 2-, 3- and 4-year LTP rates of 3.3%, 8.3%, 10.0% and 10.0%. Progression-free interval < 1 year (P = 0.002, HR = 0.375) and total number of pulmonary metastases (≥ 3) treated (P = 0.037, HR = 0.480) were independent negative prognostic factors. Thirty-day mortality rate was 0% with no intra-procedural deaths. CONCLUSION: The long-term OS and PFS following RFA for the treatment of histologically confirmed colorectal lung metastases demonstrate comparable oncological durability to surgery.

A risk model to predict 2-year survival after video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer.

OBJECTIVES: We sought to identify the risk factors associated with mortality post-video-assisted thoracoscopic surgery (VATS) lobectomy over a 2-year period. METHODS: Analysis was performed using a sample from an institutionally maintained database. All lobectomies for non-small-cell lung cancer from April 2014 to March 2018 started with VATS approach and with a complete follow-up were included (n = 732). Several clinical variables were screened using the Cox univariate analysis for their association with 2-year survival. Those with a P-value <0.1 were included in a Cox proportional hazard model. RESULTS: After multivariable analysis, the following variables showed significant association with 2-year survival: age >75 [hazard ratio (HR) 1.527, P = 0.043], carbon monoxide lung diffusion capacity <70 (HR 1.474, P = 0.061), body mass index (BMI) <18.5 (HR 2.628, P = 0.012), American Society of Anesthesiologist Physical Status >2 (HR 1.518, P = 0.047), performance status >1 (HR 1.822, P = 0.032) and male gender (HR 2.700, P < 0.001). A score of 2 was assigned to the male gender and BMI <18.5, with all other variables assigned a score of 1. Each patient was scored and placed into their risk class. A Kaplan-Meier estimate for 2-year survival was calculated for each class. These were collapsed into the following 3 classes of risk based on their similar 2-year survival: class A (score 0) 97%, 95% CI 88-99, class B (score 1-3) 84%, 95% CI 80-88, class C (score > 3) 66%, 95% CI 57-74. CONCLUSION: Our scoring system can serve as an adjunct to a clinician's experience in risk-stratifying patients during multidisciplinary tumour board discussion and the shared decision-making process.

The Impact of a Newly Established Multidisciplinary Team on the Interventional Treatment of Patients With Emphysema.

BACKGROUND: The emphysema interventional treatment involves mainly lung volume reduction surgery (LVRS) and endobronchial valve (EBV) implantation. Few institutes discuss these cases at a dedicated emphysema multidisciplinary team (MDT) meeting. OBJECTIVES: To investigate the impact of a newly established dedicated emphysema MDT meeting on the interventional treatment of such patients. METHODS: During a study period of 4 years, the outcome of 44 patients who underwent intervention according to the proposal of the emphysema MDT (group A) was compared with the outcome of 44 propensity score matched patients (group B) treated without the emphysema MDT proposal. RESULTS: More LVRS and less EBV insertions were performed in group A (P = .009). In group B, the interventions were performed sooner than in group A (P = .003). Postoperative overall morbidity and length of in-hospital stay were similar in the 2 groups (P = .918 and .758, respectively). Improvement of breathing ability was reported in more patients from group A (P = .012). In group B, the total number of re-interventions was higher (P = .001) and the time to re-intervention had the tendency to be less (P = .069). Survival was similar between the 2 groups (P = .884). Intervention without discussion at the MDT and EBV as initial intervention was an independent predictor of re-intervention. CONCLUSIONS: Interventional treatment for patients with chronic obstructive pulmonary disease (COPD) after discussion at a dedicated MDT involved more LVRS performed, required fewer interventions for their disease, and had longer re-intervention-free intervals and better breathing improvement.