Impaired Lung Function and Lung Cancer Incidence: A Nationwide Population-based Cohort Study

( Hye Seon Kang ),( Sung Kyoung Kim ),( Seung Hyun Ko ),( Seung Hoon Kim ),( Shin Young Kim ),( Chi Hong Kim ),( Kyungdo Han ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background It is unclear whether the presence of minimal lung function impairment is an independent risk factor for development of lung cancer in general populations. Methods We conducted a population-based cohort study using a nationwide database. Of 40,279 participants surveyed between 2008 and 2016, we enrolled 20,553 adult participants over 40 years of age who had undergone spirometry tests and who had never been diagnosed with any malignancy. The primary endpoint was newly diagnosed lung cancer. Results Of 20,553 participants, 169 were diagnosed with lung cancer during the follow-up period (median follow-up period of 6.5 years). The risk of lung cancer was significantly increased in participants with obstructive lung function impairment (adjusted hazard ratio (aHR) 2.51 and 95% confidence interval (CI) 1.729-3.629) in comparison to those with normal lung function. The lower was the quartile or decile of forced expiratory volume in one second (FEV1) or the FEV1/forced vital capacity (FVC) ratio, the significantly higher was the incidence rate of lung cancer (p for trend < 0.0001). With FEV1 values in the lowest quartile (Q4), the incidence of lung cancer was significantly increased regardless of FVC (FEV1 Q4 and FVC values in the higher three quartiles Q1-3: aHR 1.754; 95% CI 1.084-2.847, FEV1 Q4 and FVC Q4: aHR 1.889; 95% CI 1.331-2.681). However, when only FVC values were in the lowest quartile, there was no significant difference in the incidence rate of lung cancer. Conclusion Findings from this nationally representative, Korean population-based database show that minimal lung function impairment, as expressed by lower FEV1 or FEV1/FVC value, are significantly associated with increased incidence of lung cancer.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity

서훈녕,박소현,유현지,김지영,김태성,이종목,김문수,양희철,김석기 대한핵의학회 2019 핵의학 분자영상 Vol.53 No.6

Purpose This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer. Methods A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV1) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT. Results The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV1 showed significant correlation with ppoFEV1 based on lung perfusion SPECT and perfusion scan. Conclusions We suggest SPECT/CTas the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

폐용적과 폐기능 환기장애에 대한 유의성 평가

김지율,예수영 한국방사선학회 2023 한국방사선학회 논문지 Vol.17 No.5

To In this study, we sought to evaluate related factors affecting lung volume and their significance in pulmonary function and ventilation disorders. As experimental subjects, 206 normal adult men and women who underwent a low-dose chest CT scan and a spirometry test were selected at the same time. The experimental method was to measure lung volume using lung CT images obtained through a low-dose chest CT scan using deep learning-based AVIEW. Measurements were made using the LCS automatic diagnosis program. In addition, the results of measuring lung function were obtained using a spirometer, and gender and BMI were selected as related factors that affect lung volume, and significance was evaluated through an independent sample T-test with lung volume. As a result of the experiment, it was confirmed that in evaluating lung volume according to gender, all lung volumes of men were larger than all lung volumes of women. he result of an independent samples T-test using the respective average values ​​for gender and lung volume showed that all lung volumes were larger in men than in women, which was significant (p<0.001). And in the evaluation of lung volume according to BMI index, it was confirmed that all lung volumes of adults with a BMI index of 24 or higher were larger than all lung volumes of adults with a BMI index of less than 24. However, the independent samples T-test using the respective average values ​​for BMI index and lung volume did not show a significant result that all lung volumes were larger in BMI index 24 or higher than in BMI index less than 24 (p<0.055). In the evaluation of lung volume according to the presence or absence of pulmonary ventilation impairment, it was confirmed that all lung volumes of adults with normal pulmonary function ventilation were larger than all lung volumes of adults with pulmonary ventilation impairment. And as a result of the independent sample T-test using the respective average values ​​for the presence or absence of pulmonary ventilation disorder and lung volume, the result was significant that all lung volumes were larger in adults with normal pulmonary function ventilation than in adults with pulmonary function ventilation disorder (p <0.001). Lung volume and spirometry test results are the most important indicators in evaluating lung health, and using these two indicators together to evaluate lung function is the most accurate evaluation method. Therefore, it is expected that this study will be used as basic data by presenting the average lung volume for adults with normal ventilation and adults with impaired lung function and ventilation in similar future studies on lung volume and vital capacity testing.

기관지폐이형성증 영아에서 폐기능 측정의 유용성

김경원,최봉석,이용주,은호선,박국인,남궁란,이철,김규언,손명현 대한 소아알레르기 호흡기학회 2010 Allergy Asthma & Respiratory Disease Vol.20 No.1

목 적:건강한 미숙아에서 기관지폐이형성증을 가진 미숙아에 이르기까지 미숙아의 폐기능은 다양한 정도로 감소되어 있다고 알려져 있다. 영아에서 폐기능을 평가하는 방법은 오랜 노력 끝에 표준화되기에 이르렀으나 국내에서 아직까지 연구된 바 없다. 본 연구에서는 만성 폐질환을 가진 미숙아에서 폐기능을 객관적인 평가방법을 통하여 측정하고 폐기능 감소에 영향을 미치는 위험 요인들을 분석하여 그 유용성을 알아보고자 하였다. 방 법:세브란스 어린이병원에서 출생한 54명을 대상으로 하였다. 전체 대상아 중 남자는 31명, 여자는 23명이었고, 평균연령은 5.6±3.7개월이었다. 대상자에서 영아폐기능 측정기구(Exhalyser; EcoMedics, Dürnten, Switzerland)를 이용하여 일회호흡량(tidal volume, TV) 및 기능적잔기량(functional Residual Capacity, FRC)을 측정하였고, 기관지확장제 흡입 후 같은 방법으로 측정하여 변화를 관찰하였다. 전체 대상아에서 검사와 관련된 부작용은 없었다. 결 과:대상 환아 54명 중 22명은 재태주령 28주 미만 출생아, 25명은 28주 이상 33주 미만 출생아, 7명은 33주 이상 37주 미만의 출생아였다. 또한 초극소 저체중출생아 23명, 극소 저체중출생아 23명, 저체중출생아는 8명이었다. 기관지확장제 흡입 전후 기능적잔기량 변화(delta FRC, dFRC)는 재태주령이 어릴수록(P<0.05), 출생체중이 작을수록(P<0.05) 의미있게 증가하였다. 기능적잔기량 변화는 재태주령(r=-0.35; P=0.013), 출생체중(r=-0.32; P=0.026)과 유의한 음의 상관관계를, 기계호흡일수(r= 0.42; P=0.0028), 산소치료일수(r=0.43; P=0.0024)와는 양의 상관관계를 보였다. 기관지확장제 흡입 전 기능적잔기량은 출생체중이 작을수록 유의하게 작았으며,(r=0.43; P=0.0013) 기관지확장제 흡입 전 일회호흡량은 기계호흡일수와 음의 상관관계를 나타내었다.(r=-0.39; P= 0.0048)결 론:미숙아에서 출생체중이 작을수록, 재태주령이 어릴수록, 기계호흡일수와 산소치료일수가 길수록 기관지확장제에 의한 기능적잔기량의 가역성이 증가하였다. 기능적잔기량 가역성은 만성 폐질환 미숙아에서 안전하게 측정할 수 있는 유용한 폐기능 지표로 생각된다. Purpose:Pulmonary function is decreased in varying degrees in healthy premature infants as well as those with bronchopulmonary dysplasia. The evaluation of pulmonary function in infants is finally standardized after strenuous efforts, but it has not yet been in Korea. In this study, we aimed at the evaluation of the utility of pulmonary function tests in premature infants with chronic lung disease by objectively measuring pulmonary function and by analyzing the risk factors that may decrease lung function. Methods:Fifty-four premature infants born in Severance Hospital were selected. Among the 54 infants, 31 were male and 23 were female, and their mean age was 5.6±3.7 years. Exhalyser was used to measure tidal volume and functional residual capacity, and then their change after the inhalation of bronchodilators was evaluated. There was no test related complication in all subjects. Results:Among the 54 subjects, 22 were at the gestational age of <28 weeks, 25 were at the gestational age between 28 and 33 weeks, and 7 were at the gestational age between 33 and 37 weeks. As for birth weight, 23 had extreme low birth weight, 23 had very low birth weight, and 8 had low birth weight. The delta functional residual capacities (FRCs) before and after the inhalation of bronchodilator were significantly increased in infants with younger gestational age (P<0.05) and lower birth weight (P<0.05). There was a significant negative correlation between gestational age and birth weight, and a significant positive correlation with the duration of ventilator care and that of oxygen therapy. The delta FRC before the inhalation of bronchodilator was significantly lower in infants with lower birth weight, and the tidal volume before the inhalation of bronchodilator correlated negatively with the duration of ventilator care. Conclusion:The reversibility of FRC is increased in premature infants with lower birth weight, younger gestational age, and longer duration of ventilator care and oxygen therapy. The reversibility of FRC may be a useful parameter of pulmonary function that can be safely measured in premature infants with chronic lung disease.

기관지폐이형성증 영아에서 폐기능 측정의 유용성

김경원 ( Kyung Won Kim ),최봉석 ( Bong Seok Choi ),이용주 ( Yong Ju Lee ),은호선 ( Ho Seon Eun ),손명현 ( Myung Hyun Sohn ),박국인 ( Kook In Park ),남궁란 ( Gung Ran Nam ),이철 ( Chul Lee ),김규언 ( Kyu Earn Kim ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2010 소아알레르기 및 호흡기학회지 Vol.20 No.1

목적: 건강한 미숙아에서 기관지폐이형성증을 가진 미숙아에 이르기까지 미숙아의 폐기능은 다양한 정도로 감소되어 있다고 알려져 있다. 영아에서 폐기능을 평가하는 방법은 오랜 노력 끝에 표준화되기에 이르렀으나 국내에서 아직까지 연구된 바 없다. 본 연구에서는 만성 폐질환을 가진 미숙아에서 폐기능을 객관적인 평가방법을 통하여 측정하고 폐기능 감소에 영향을 미치는 위험 요인들을 분석하여 그 유용성을 알아보고자 하였다. 방법: 세브란스 어린이병원에서 출생한 54명을 대상으로 하였다. 전체 대상아 중 남자는 31명, 여자는 23명이었고, 평균연령은 5.6±3.7개월이었다. 대상자에서 영아폐기능 측정기구(Exhalyser; EcoMedics, Du rnten, Switzer-land)를 이용하여 일회호흡량(tidal volume, TV) 및 기능적잔기량(functional Residual Capacity, FRC)을 측정하였고, 기관지확장제 흡입 후 같은 방법으로 측정하여 변화를 관찰하였다. 전체 대상아에서 검사와 관련된 부작용은 없었다. 결과: 대상 환아 54명 중 22명은 재태주령 28주 미만 출생아, 25명은 28주 이상 33주 미만 출생아, 7명은 33주 이상 37주 미만의 출생아였다. 또한 초극소 저체중출생아 23명, 극소 저체중출생아 23명, 저체중출생아는 8명이었다. 기관지확장제 흡입 전후 기능적잔기량 변화(delta FRC, dFRC)는 재태주령이 어릴수록(P<0.05), 출생체중이 작을수록(P<0.05) 의미있게 증가하였다. 기능적잔기량 변화는 재태주령(r=-0.35; P=0.013), 출생체중(r=-0.32; P=0.026)과 유의한 음의 상관관계를, 기계호흡일수(r=0.42; P =0.0028), 산소치료일수(r=0.43; P =0.0024)와는 양의 상관관계를 보였다. 기관지확장제 흡입 전 기능적잔기량은 출생체중이 작을수록 유의하게 작았으며, (r=0.43;P=0.0013) 기관지확장제 흡입 전 일회호흡량은 기계호흡일수와 음의 상관관계를 나타내었다. (r=-0.39; P=0.0048) 결론: 미숙아에서 출생체중이 작을수록, 재태주령이 어릴수록, 기계호흡일수와 산소치료일수가 길수록 기관지확장제에 의한 기능적잔기량의 가역성이 증가하였다. 기능적잔기량 가역성은 만성 폐질환 미숙아에서 안전하게 측정할 수 있는 유용한 폐기능 지표로 생각된다. Purpose: Pulmonary function is decreased in varying degrees in healthy premature infants as well as those with bronchopulmonary dysplasia. The evaluation of pulmonary function in infants is finally standardized after strenuous efforts, but it has not yet been in Korea. In this study, we aimed at the evaluation of the utility of pulmonary function tests in premature infants with chronic lung disease by objectively measuring pulmonary function and by analyzing the risk factors that may decrease lung function. Methods: Fifty-four premature infants born in Severance Hospital were selected. Among the 54 infants, 31 were male and 23 were female, and their mean age was 5.6±3.7 years. Exhalyser was used to measure tidal volume and functional residual capacity, and then their change after the inhalation of bronchodilators was evaluated. There was no test related complication in all subjects. Results: Among the 54 subjects, 22 were at the gestational age of <28 weeks, 25 were at the gestational age between 28 and 33 weeks, and 7 were at the gestational age between 33 and 37 weeks. As for birth weight, 23 had extreme low birth weight, 23 had very low birth weight, and 8 had low birth weight. The delta functional residual capacities (FRCs) before and after the inhalation of bronchodilator were significantly increased in infants with younger gestational age (P<0.05) and lower birth weight (P<0.05). There was a significant negative correlation between gestational age and birth weight, and a significant positive correlation with the duration of ventilator care and that of oxygen therapy. The delta FRC before the inhalation of bronchodilator was significantly lower in infants with lower birth weight, and the tidal volume before the inhalation of bronchodilator correlated negatively with the duration of ventilator care. Conclusion: The reversibility of FRC is increased in premature infants with lower birth weight, younger gestational age, and longer duration of ventilator care and oxygen therapy. The reversibility of FRC may be a useful parameter of pulmonary function that can be safely measured in premature infants with chronic lung disease. [Pediatr Allergy Respir Dis(Korea) 2010;20:68-75]

말기 폐기종 환자에서 기능적 기준에 의한 일측 폐이식술

조현민,백효채,김도형,강두영,이두연 대한흉부외과학회 2003 Journal of Chest Surgery (J Chest Surg) Vol.36 No.2

The Single Lung Transplantation for End-Stage Emphysema by Functional Criteria 말기 폐기종 환자에 대한 치료로 폐이식이 가장 효과적인 방법으로 받아들여지고 있으나 장기 공여자를 구하기가 쉽지 않고 다른 장기에 비해 비교적 건강한 폐를 얻기가 매우 어려운데다가 키와 몸무게, 흉곽크기 등을 고려한 장기 크기의 적합성을 맞추기는 더욱 힘들다. 공여자의 폐가 절대적으로 부족한 상황에서 일측 폐이식술이 양측 폐이식술에 비해 많이 시행되고 있는 추세이며 수술 결과에 따른 장기 생존율에 있어서도 큰 차이가 없는 것으로 보고되고 있다. 최근에는 폐이식 수술 시 흉곽크기 등을 고려한 장기 크기 측정보다는 기능적 기준으로서 나이, 성별, 키를 변수로 한 예측 총폐활량이 보다 적절한 평가방법으로 받아들여지고 있다.1.Hosenpud JD, Bennett LE, Keck BM, Fiol B, Boucek MM, Novick RJ. The Registry of the International Society for Heart and Lung Transplantation: sixteenth report-1999. J Heart Lung Transplant 1999;18:611-26.2.Weill D, Kshavjee S. Lung Transplantation for Emphysema: Two Lungs or One. J Heart Lung Transplant 2001;20:739-42.3.Gammie JS, Keenan RJ, Pham SM, et al. Single versus double lung transplantation for pulmonary hypertension. J Thorac Cardiovasc Surg 1998;115:397-403.4.신화균, 김해균, 이두연 등. 폐기종 환자에서의 우측 폐이식술. 대흉외지 2000;33:585-9.5.류송현, 김해균, 이두연 등. 이형 혈액형에서 시행한 폐이식술. 대흉외지 2001;34:94-6.6.Meyer DM, Bennet LE, Novick RJ, Hosenpud JD. Single vs Bilateral, Sequential Lung Transplantation for End- Stage Emphysema: Influence of Recipient Age on Survival and Secondary End-points. J Heart Lung Transplant 2001; 20:935-941. 7. Miyoshi S, Demertzis S, Eckstein F, Hohlfeld J, Schaefers HJ. Chest size matching in single and double lung transplantation. Jpn J Thorac Cardiovasc Surg 1999;47(4): 163-70.8.Hayden AM, Scarlett MV, Fox K. Relationship between donor/recipient lung size mismatch and functional outcome in single lung transplantation for COPD. J Transpl Coord 1996;6(3):155-8.

폐절제술후의 폐기능 예측에 대한 나선식 정량적 CT의 유용성 (나선식 정량적 CT와 폐관류스캔과의 비교)

이조한 대한흉부심장혈관외과학회 2000 Journal of Chest Surgery (J Chest Surg) Vol.33 No.10

Background : the prediction on changes in the lung function after lung surgery would be an important indicator in terms of the operability and postoperative complications. In order to predict the postoperative FEV1 - the commonly used method for measuring changes in lung function- a comparison between the quantitative CT and the perfusion lung scan was made and proved its usefulness. Material and Method : The subjects included 22 patients who received perfusion lung scan and quantitative CT preoperatively and with whom the follow-up of PFT were possibles out of the pool of patients who underwent right lobectomy or right pneumonectomy between June of 1997 and December of 1999. The FEV1 and FVC were calibrated by performing the PFT on each patient and then the predicted FEV1 and FVC were calculated after performing perfusion lung scan and quantitative CT postoperatively. The FEV1 and FVC were calibrated by performing the PFT after 1 week and after 3 momths following the surgery. Results : There was a significant mutual scan and the actual postoperative FEV1 and FVC at 1 week and 3 months. The predicted FEV1 and FVC(pneumonectomy group : r=0.962 and r=0.938 lobectomy group ; r=0.921 and r=913) using quantitative CT at 1 week postoperatively showed a higher mutual relationship than that predicted by perfusion lung scan(pneumonectomy group : r=0.927 and r=0.890 lobectomy group : r=0.910 and r=0.905) The result was likewise at 3 months postoperatively(CT -pneumonectomy group : r=0.799 and r=0.882 lobectomy group : r=0.934 and r=0.932) Conclusion ; In comparison to perfusion lung scan quantitative CT is more accurate in predicting lung function postoperatively and is cost-effective as well. Therefore it can be concluded that the quantitative CT is an effective method of replacing the perfusion lung scan in predicting lung function post-operatively. However it is noted that further comparative analysis using more data and follow-up studies of the patients is required.

F-4 The factors related with lung function recovery at the first year of lung transplantation

윤보라,( Ji Eun Park ),( Chi Young Kim ),( Moo Suk Park ),( Young Sam Kim ),( Kyung Soo Chung ),( Joo Han Song ),( Hyo-chae Paik ),( Jin Gu Lee ),( Song Yee Kim ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Background: Post-operative pulmonary function test is one of the most important prognostic factors. The purpose of this study was to figure out the factors which affect on the FEV1 at the first year after lung transplantation (LTx). Method: We retrospectively reviewed the medical records of the LTx patients a tertiary-care center between October, 2012 and December, 2015. The patients who survived more than one year and performed pulmonary function test more than three times were enrolled. The patients were divided into two groups according to 1 year post-operative FEV1 (≤80% vs. >80%). We compared two groups and analyzed the factors related with lung function recovery. Results: 58 patients were enrolled in this study; 28 (48%) patients recovered FEV1 more than 80% and 30 (52%) did not. The data shows that younger recipients, longer hospitalization and intensive care unit stay, prolonged mechanical ventilator use, tracheostomy, lower PaO2/FiO2, high grade primary graft failure, longer operation time, higher amount of RBC transfusion during operation were related with not full recovery of lung function. Conclusions: Immediate postoperative status may be related with recovery of lung function after LTx.

Association between the Risk of Obstructive Sleep Apnea and Lung Function: Korea National Health and Nutrition Examination Survey

( Jinwoo Seok ),( Hee-young Yoon ) 대한결핵 및 호흡기학회 2024 Tuberculosis and Respiratory Diseases Vol.87 No.3

Background: Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with various health issues. Although some studies have suggested an association between reduced lung function and OSA, this association remains unclear. Our study aimed to explore this relationship using data from a nationally representative population-based survey. Methods: We performed an analysis of data from the 2019 Korea National Health and Nutrition Examination Survey. Our study encompassed 3,675 participants aged 40 years and older. Risk of OSA was assessed using the STOP-Bang (Snoring, Tiredness during daytime, Observed apnea, and high blood Pressure-Body mass index, Age, Neck circumference, Gender) questionnaire and lung function tests were performed using a portable spirometer. Logistic regression analysis was applied to identify the risk factors associated with a high-risk of OSA, defined as a STOP-Bang score of ≥3. Results: Of 3,675 participants, 600 (16.3%) were classified into high-risk OSA group. Participants in the high-risk OSA group were older, had a higher body mass index, and a higher proportion of males and ever-smokers. They also reported lower lung function and quality of life index in various domains along with increased respiratory symptoms. Univariate logistic regression analysis indicated a significant association between impaired lung function and a high-risk of OSA. However, in the multivariable analysis, only chronic cough (odds ratio [OR], 2.413; 95% confidence interval [CI], 1.383 to 4.213) and sputum production (OR, 1.868; 95% CI, 1.166 to 2.992) remained significantly associated with a high OSA risk. Conclusion: Our study suggested that, rather than baseline lung function, chronic cough, and sputum production are more significantly associated with OSA risk.

Relevance of Dental Health Capacity and Pulmonary Function Status in Adults

송귀숙,류다영,김인자 한국치위생과학회 2017 치위생과학회지 Vol.17 No.5

The purpose of this study was to confirm the relevance of dental health capacity and pulmonary function status. The subjects of this study wereadults aged 40 years and older, who participated in pulmonary function and oral examinations. The data used for this study were raw data fromthe sixth Korea National Health and Nutrition Examination Survey (2013∼2015). Statistical analysis was performed by analysis of complex samplesurvey data. The results were as follows: First, restrictive and obstructive patterns were more prevalent among males than females. They were evenworse in older subjects. Approximately 67% of smokers had obstructive pattern. Second, there was a relevance between dental health capacityand pulmonary function status. The functioning teeth index, number of present teeth, and number of sound teeth (ST), which are indicators of dentalhealth, declined with decreased pulmonary function. The number of missing teeth (MT) increased as the pulmonary function deteriorated (p<0.05). Third, the relevance between dental health capacity and pulmonary function status after stratifying the life-long smoking experience was statisticallysignificant in the tissue health (T-health) index and ST among non-smokers. The relevance between dental health capacity and pulmonary functionstatus after stratifying the life-long smoking experience was statistically significant (p<0.05) for the T-health index, ST, and MT among smokers. However, there was no relevance between dental health capacity and pulmonary function status after stratifying the life-long smoking experienceand adjusting confounding variables. In conclusion, there was a relevance between dental health capacity and pulmonary function status afterconfounding variables were adjusted. However, there was no relevance between dental health capacity and pulmonary function status afterstratifying the life-long smoking experience and adjusting confounding variables.