Collection methods of exhaled volatile organic compounds for lung cancer screening and diagnosis: a systematic review
Review Article

Collection methods of exhaled volatile organic compounds for lung cancer screening and diagnosis: a systematic review

Yuhang He1,2# ORCID logo, Zhixia Su3#, Taining Sha3# ORCID logo, Xiaoping Yu1, Hong Guo4, Yujian Tao5, Liting Liao6, Yanyan Zhang7, Guotao Lu8,9, Guangyu Lu3, Weijuan Gong4,6,8

1Department of Health Management Center, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; 2School of Nursing, Medical College of Yangzhou University, Yangzhou University, Yangzhou, China; 3School of Public Health, Medical College of Yangzhou University, Yangzhou University, Yangzhou, China; 4Department of Thoracic Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; 5Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; 6Department of Basic Medicine, Medical College of Yangzhou University, Yangzhou University, Yangzhou, China; 7Testing Center of Yangzhou University, Yangzhou University, Yangzhou, China; 8Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; 9Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China

Contributions: (I) Conception and design: Y He, Z Su, T Sha, Guangyu Lu, W Gong; (II) Administrative support: X Yu, H Guo, Y Tao, Guotao Lu, W Gong; (III) Provision of study materials or patients: X Yu, H Guo; (IV) Collection and assembly of data: Y He, Z Su, T Sha, Y Zhang, L Liao; (V) Data analysis and interpretation: Y He, Z Su, T Sha, Guangyu Lu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work as co-first authors.

Correspondence to: Weijuan Gong, MD. Department of Thoracic Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou 225100, China; Department of Basic Medicine, Medical College of Yangzhou University, Yangzhou University, No. 136 Jiangyang Middle Road, Yangzhou 225009, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou 225100, China. Email: wjgong@yzu.edu.cn.

Background: The identification of volatile organic compounds (VOCs) in exhaled breath has garnered significant research attention as a means of screening and diagnosing lung cancer in recent decades. However, there is no universally accepted protocol for the collection of breath samples to measure VOCs in the clinical context. The purpose of this study was to summarize the current sampling techniques used to obtain VOCs from exhaled breath specifically in the context of lung cancer screening and diagnosis.

Methods: We searched four major literature databases (PubMed, Embase, Web of Science, and The Cochrane Library) to identify studies published from January 1985 to October 2023. Trials that analyzed endogenous VOCs within exhaled breath to screen or diagnose lung cancer were included. The methods used for exhaled breath collection were divided under the following headings: before collection (patient preparation, environmental preparation, contamination detection), during collection (time of breath collection, type of container, breath fraction selected, the volume and route of breath), and after collection (storage of breath samples, VOCs stability).

Results: A total of 89 studies involving 6,409 individuals diagnosed with lung cancer were selected. The methods used to collect the breath varied substantially among the studies. A separate room was prepared for breath collection in 29 studies, the physiological state of the participants was described in 57 studies, and environmental considerations were reported in 41 studies. Polymer bags, specifically Tedlar bags, were the predominant choice for breath sample collection and were used in 58 out of the 89 studies. Alveolar breath was the most commonly selected breath fraction, which was used in 43 studies. Only 15 studies reported the storage conditions of the breath samples, which ranged from −40 ℃ to room temperature, and the stability of VOCs was recorded in 41 studies.

Conclusions: There is an urgent need for breath collection methods to be standardized to maximize the potential of this diagnostic approach. The summarized exhaled breath collection process proposed in this study based on included studies may serve as a method for future clinical research.

Keywords: Lung cancer; volatile organic compounds (VOCs); breath collection method

Submitted Jun 24, 2024. Accepted for publication Oct 24, 2024. Published online Nov 29, 2024.

doi: 10.21037/jtd-24-1001

Highlight box

Key findings

• The methods used to collect the breath varied substantially among the current lung cancer studies. Variability in the results of breath collection may result from the physiological condition of the individual, environmental considerations, contamination detection, the choice of collection container, the breath fraction collected, the volume of breath, the storage of breath samples and the stability of the target volatile organic compounds (VOCs).

What is known and what is new?

• There is no universally accepted protocol for the collection of breath samples to measure VOCs in the clinical context.

• We summarize the methods that have been used to collect exhaled breath to screen or diagnose lung cancer in existing clinical studies, a breath collection process which was divided under the following headings: before collection (patient preparation, environmental preparation, contamination detection), during collection (time of breath collection, type of container, the volume and route of breath, and breath fraction selected), and after collection (storage of breath samples, VOCs stability), will be proposed based on the existing evidence.

What is the implication, and what should change now?

• This study aims to draw the attention of researchers to the importance of standardizing breath collection methods in future clinical trials, and provide a summary of the methods that have been used for breath collection thus far, which may facilitate better standardization of breath collection in future studies.

Introduction

Background

Lung cancer has the second highest incidence and the highest rate of mortality of all malignant tumors (1). Around 85% of patients with lung cancer are diagnosed at an advanced stage, and the five-year survival rate is as low as 10–20% (2). Therefore, early lung cancer detection is a crucial factor for increasing survival among individuals with this condition. Lung cancer detection and diagnosis mainly rely on computed tomography (CT), chest X-ray, low-dose CT, and biopsy. However, considering the disadvantages of these diagnostic methods, such as their invasiveness, high false-positive rate, and radiation exposure risk (3-5), several studies have explored the value of exhaled breath analysis for the screening and early diagnosis of lung cancer in recent decades (6-11). Breath collection is non-invasive, samples are easily available, and it has high acceptability (12). Since Gordon et al. first used gas chromatography-mass spectrometry (GC-MS) to detect volatile organic compounds (VOCs) in patients with lung cancer in 1985 (13), several researchers have demonstrated that the exhaled VOCs of patients with lung cancer are significantly different from that of patients with other pulmonary diseases and healthy control subjects (6,9,10,14-17). Therefore, breath analysis has great potential for the early screening and diagnosis of lung cancer (18).

Differences in collection methods

The methods used for breath collection vary greatly among published studies, which may lead to inconsistent results. For instance, Poli et al. observed elevated isoprene in the exhaled breath of individuals with lung cancer compared with healthy individuals when using the Bio-VOC breath sampler to collect alveolar breath (19). Bajtarevic et al. arrived at the opposite conclusion when using the Tedlar bag to collect mixed breath (20).

Variability in the results of breath collection may also result from the physiological condition of the individual, the choice of collection container, the breath fraction collected, the storage of breath samples and the stability of the target VOCs, amongst other factors. For example, some studies required participants to fast for 8–12 hours before breath collection (11,21-23), while Peng et al. only instructed participants to avoid coffee and alcohol consumption rather than requesting them to fast completely (24). Regarding the choice of collection container, some researchers utilized polymer bags for breath collection, such as Tedlar bags or Mylar bags (9,25-28). Others chose Bio-VOC breath samplers (29-31), while some studies preferred portable breath sample collection devices or self-made collection devices (22,32,33). Regarding the breath fraction collected, many researchers selected alveolar breath as the sampled breath fraction (6,8,34,35), while others utilized mixed breath as the sampled breath fraction (11,28,36). As for the stability of the target VOCs, some studies stored breath samples at room temperature (25,37), some stored the samples in an incubator at 4 ℃ (21,38), and some chose to store the samples at −40 ℃ (39,40), indicating further variability.

Objective

It is well acknowledged that standardizing the breath collection method is crucial for the dissemination of research findings, as well as for promoting the clinical utilization of this non-invasive method of breath testing in real clinical contexts. In this review, we summarize the methods that have been used to collect exhaled breath to screen or diagnose lung cancer in existing clinical studies. Moreover, a breath collection process will be proposed based on the existing evidence. The present study aims to draw the attention of researchers to the importance of standardizing breath collection methods in future clinical trials. Moreover, this study aims to provide a summary of the methods that have been used for breath collection thus far, which may facilitate better standardization of breath collection in future studies. We present this article in accordance with the PRISMA reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1001/rc).

Methods

Literature search

This study was registered in PROSPERO (No. CRD42023407693). To identify relevant articles, we performed an electronic search of four major literature databases: PubMed, Embase, Web of Science, and The Cochrane Library. The search period was from January 1985 to October 2023. The search terms used in combination were “lung neoplasms”, “lung cancer”, “volatile organic compounds”, “VOCs”, “breath”, and “exhaled”. The Boolean operators “AND” and “OR” were applied. The search was restricted to English-language studies involving humans. Conference abstracts were not considered. The detailed search strategy is described in Appendix 1.

Inclusion and exclusion criteria

Two reviewers (Y.H., Z.S.) carefully screened the titles and abstracts of the studies identified through the electronic literature search. The full texts of potentially relevant articles were evaluated to determine their eligibility for inclusion. Studies were required to satisfy the following criteria to be deemed eligible for inclusion: (I) screened or diagnosed lung cancer and (II) analyzed exhaled breath. Studies were excluded if they (I) were not conducted in humans; (II) solely analyzed biofluids, such as urine, blood, and/or feces; (III) were not published in the English language; or (IV) did not mention the methods used for breath collection. Moreover, the reference lists of the included studies were manually searched to identify any additional relevant studies. Figure 1 portrays the process of identification, screening, eligibility assessment, and selection in accordance with the PRISMA guidelines.

Figure 1 Flowchart of study selection.

Data extraction

To gather information on the studies of interest, we created standardized tables. Table 1 provides the references for each individual study. All details regarding the collection of exhaled VOCs in the included studies can be found in Appendix 2. Two independent reviewers (Y.H., T.S.) carefully examined the complete texts of the selected studies. The reviewers extracted qualitative data from each study and recorded it in a Microsoft Excel spreadsheet. Information, such as the authors, publication dates, number of studies included, physiological condition of the patients, environmental considerations, sampling periods, containers used to store the breath samples, breath fractions used, the volume and route of breath, storage conditions of breath samples and the stability of VOCs was extracted from the selected studies. In cases of disagreement about whether a study met the inclusion criteria, group discussions were held with a third investigator (Guangyu Lu) until consensus was reached.

Table 1

Methods used to collect exhaled breath

Author, year Before collection During collection After collection
Specific room for breath collection Contamination detection Physiological conditions Sampling time Brief description Breath collection containers Fraction of breath selected Volume Route Ambient air Storage conditions Stability
of VOCs
Phillips et al., 1999 (41) NR NR Fast overnight within 24 h Before bronchoscopy Wear a nose clip while breathing in and out of the device, via a disposable mouthpiece, for 5 min Portable breath collection apparatus Alveolar breath 10 L Mouth NR NR NR
Yu et al., 2005 (42) NR Bags were cleaned with acetone and thoroughly rinsed several times with deionized water, and then filled with purified nitrogen and dried at 80 ℃ for 12 h to remove any residual acetone NR NR NR Tedlar bag NR NR NR NR NR NR
Phillips et al., 2007 (32) NR NR NR NR Breathe normally through the disposable mouthpiece of a portable breath collection apparatus for 2.0 min Portable breath collection apparatus Alveolar breath 1 L Mouth C NR NR
Wehinger et al., 2007 (43) NR Before collection, bags were rinsed with pure nitrogen two to three times, then heated over night at 95 ℃ filled with flushing gas, and finally re-rinsed two to three times before being depleted and stored NR NR Breathe normally Tedlar bag Mixed breath 3 L NR C At room temperature On the day of breath sampling
Phillips et al., 2008 (44) NR NR NR NR NR Portable breath collection apparatus Alveolar breath NR NR C NR NR
Bajtarevic et al., 2009 (20) NR NR Consumed food not later than one hour before breath sampling. Sit for 5 min NR NR Tedlar bag Mixed breath NR Mouth NR NR 6 h
Gaspar et al., 2009 (45) NR NR NR NR Breathe deeply into the bag Tedlar bag NR 5 L NR NR NR 24 h
Ligor et al., 2009 (46) NR Bags were filled with nitrogen, heated at 85 ℃ for at least 8 h and then completely evacuated Did not on any special diet and did not consume food for at least one hour before breath sampling and sit for 5 min NR NR Tedlar bag Mixed breath 3 L NR C NR 3–6 h
Peng et al., 2009 (24) NR The Mylar bags were re-used and thoroughly cleaned before each use with flowing nitrogen (99.999% purity) gas for 5–8 min Did not to drink coffee or alcohol for at least 1 h and 12 h NR In a controlled manner Mylar bag Alveolar breath 750 mL Mouth NR NR 2 d
Westhoff et al., 2009 (47) NR NR NR NR NR Teflon bulb Alveolar breath NR Mouth NR NR NR
Fuchs et al., 2010 (48) Y NR After resting for 10 min NR CO2-controlled manner Evacuated sealed 20 mL headspace vial Alveolar breath 20 mL NR C NR 6 h
Poli et al., 2010 (29) NR Before being reused, the tubes were thoroughly cleaned by means of flushing with nitrogen NR NR NR Bio-VOC Alveolar breath 150 mL NR NR 4 ℃ 2 h
Kischkel et al., 2010 (49) Y NR NR NR CO2-controlled manner Gastight syringe +an evacuated sealed 20 mL headspace vial Alveolar breath 20 mL NR C NR 6 h
Song et al., 2010 (50) Y NR Fasted overnight NR NR Tedlar bag Mixed breath NR Mouth C NR NR
Tran et al., 2010 (51) NR NR NR NR NR Inert gas impermeable bag NR NR Mouth NR 4 ℃ 4 h
Buszewski et al., 2011 (52) NR Before collection, Tedlar bags were thoroughly cleaned by flushing with nitrogen. Then, the bag was filled with nitrogen and heated at 60 ℃ for several hours to remove residual contaminants NR NR CO2-controlled manner Tedlar bag Alveolar breath NR Mouth C NR NR
Rudnicka et al., 2011 (53) NR Before collection breath, all bags were cleaned by flushing with argon gas and then filled with argon and heated at 60 ℃ for 12 h to remove any contaminations NR NR NR Tedlar bag NR 1 L NR NR NR NR
Ulanowska et al., 2011 (54) NR Before collecting breath, bags were thoroughly cleaned by flushing with argon, then heated at 60 ℃ for several hours to remove residual contaminants NR NR CO2-controlled manner Tedlar bag Alveolar breath NR Mouth C NR NR
Buszewski et al., 2012 (55) NR Before collection of breath, all bags were cleaned by flushing with argon gas and then filled with argon and heated at 60 ℃ for 12 h to remove any contamination NR NR CO2-controlled manner Tedlar bag Alveolar breath 1 L Mouth C NR NR
Filipiak et al., 2014 (56) NR NR Rested for 10 min before breath collection and food consumption was not less than 2 h before collection In the morning CO2-controlled manner Tedlar bag Alveolar breath NR NR NR NR 5 h
Gi et al., 2014 (57) NR NR Before any food in-take and after gargling with purified water In the morning Breath deeply into the bag Tedlar bag NR 1.5 L Mouth NR NR NR
Ma et al., 2014 (58) NR Prior to use, Tedlar bags were used three times with dry nitrogen gas (99.99% purity) and checked for residual VOCs Refrained from eating garlic, leeks and onions or any spicy food 24 h prior to breath collection. The smokers refrained from smoking and drinkers from drinking 10 h prior to the gas sampling Between 9:30 and 11:30 am before lunch Perform a single slow vital capacity breath Tedlar bag Alveolar breath 3 L NR C NR 24 h
Phillips et al., 2015 (33) Y NR NR NR Wear a nose clip and breathe normally through a disposable valved mouthpiece and bacterial filter into the BCA for 2.0 min Portable breath collection apparatus Alveolar breath NR NR C −15 ℃ NR
Ligor et al., 2015 (59) NR Before collection of breath, all bags were cleaned to remove volatiles by flushing with argon, then stored at 60 ℃ in the laboratory oven Consumed food not later than 1 h before breath sampling. Rest for 10 min NR NR Tedlar bag Mixed breath NR NR C NR 2–8 h
Gasparri et al., 2016 (60) Y NR Fasted within 8 hours before the test, to avoid smoking the night before the test, not to eat aromatic food the day before the test, to brush teeth after the last meal taken the evening before the test; to avoid perfumes or scented soap, in the twenty-four hours before the breath test NR NR Tedlar bag Mixed breath NR Mouth NR NR Immediately
Itoh et al., 2016 (61) Y NR Did not eat or smoke for several hours before collection of samples At 6–8 weeks after surgical tumor resection NR Analytic Barrier bag Alveolar breath 1 L NR NR NR NR
Sakumura et al., 2017 (62) Y NR Did not eat or smoke for several hours and stayed in the room for at least 10 min NR NR Analytic Barrier bag Alveolar breath NR Mouth C NR NR
Cai et al., 2017 (63) NR NR Avoided certain foods with strong smells, stop smoking and chewing gum before the test. Subjects were asked to fast for at least 12 h before testing and to only consume water NR Inhale, hold breath momentarily, and then exhale Devex bag Alveolar breath 1 L Mouth NR NR Immediately
Chang et al., 2018 (25) Y The desorption tube was flushed with 99.99% pure nitrogen gas which had been flushed three times before sampling Eating, drinking, smoking, tooth-brushing with toothpaste or gargling with gargle were not allowed for minimum of 2 hour before sampling NR Take a maximum possible deep inspiration followed by take a maximum possible deep expiration, the first C breath was discarded Tedlar bag Alveolar breath NR Mouth C At room temperature Immediately
Huang et al., 2018 (26) NR Each bag was flushed with nitrogen five times and then heated to 45 ℃ for approximately 12 h Avoided eating and smoking for 12 h before the air sampling After intubation with an endotracheal tube and before surgery CO2-controlled manner Tedlar bag Alveolar breath 1 L NR NR NR 2 h
Yu et al., 2018 (64) NR Before collection, bags was cleaned by flushing with nitrogen gas to get rid of any con taminations Cleaned their mouth with water and breathed for more than 30 min before sampling NR NR Tedlar bag NR NR NR NR The C breath samples were placed inside an opaque box to avoid possible photooxidation of volatiles before analysis 24 h
Li et al., 2019 (39) NR NR NR NR Take a normal inhalation, exhale three times Bio-VOC + Tedlar bag Alveolar breath 500 mL Mouth C −40 ℃ 7 d
Pesesse et al., 2019 (65) NR Before sampling, Tedlar bags were flushed twice with nitrogen (purity >99.99%) to decrease residual contaminants NR January/
March/May		 NR Tedlar bag NR 5 L NR NR NR 2 h
Rudnicka et al., 2019 (66) NR Before collection of breath, all bags were cleaned by flushing with argon gas and then filled with argon and heated at 60 ℃ for 12 h to remove any contaminants Avoided eating and drinking NR CO2-controlled manner A breath sampler + Tedlar bag Alveolar breath 1 L NR C NR 3–4 h
Chen et al., 2020 (67) Y NR Consumed no food at least 3 h and had not taken alcohol, tobacco, or coffee at least 24 h before sampling NR Exhale half of the breath to the atmosphere to make sure that only end-tidal breath is exhaled into the sampling bag FEP gas sampling bag Alveolar breath 2 L Mouth C NR NR
Gashimova et al., 2020 (37) Y Sampling bags previously cleaned by flushing with nitrogen gas Consumed food no later than 1 h before breath sampling and did not smoke for at least 2.5 h before breath sampling, then rested for 10 min in a sampling room NR Deeply breathe, hold breath for 10 s and breathe out into the bag in a calm manner Tedlar bag Mixed breath 5 L NR C At room temperature 6 h
Koureas et al., 2020 (68) Y Before use, Tedlar bags were flushed with pure nitrogen to remove any contamination NR NR Inhale deeply and hold breath for 30 s, then exhale Tedlar bag NR 1 L Mouth C NR 6 h
Li et al., 2020 (69) NR Tedlar bags were cleaned with pure nitrogen three times before use Fasted overnight and smokers were asked to cease smoking 2 h before sampling NR Inhale deeply and exhale Tedlar bag NR 2 L Mouth C NR 6 h
Saidi et al., 2020 (21) NR Tedlar bag was cleaned 3–5 times with nitrogen flow before and after any breath collection Did not to use medication, drugs or alcohol, and not to drink beverages, food or tobacco more than twelve hours before breath collection NR NR Bio-VOC + Tenax TA sorbent tubes, Tedlar bag Alveolar breath NR NR NR 4 ℃ NR
Chen et al., 2021 (70) Y NR Fasted after 8 pm the night before gas collection, gargled with clean water for 2–3 times before sampling From 7:00 to 8:00 am Wear a nose clip and take deep inspiration Tedlar bag NR 2 L Mouth C NR NR
Gashimova et al., 2021 (27) Y Bags were previously cleaned by flushing with nitrogen gas Had a 10 min rest in a room NR Breathe deeply, hold breath for 10 s and breathe out into the sampling bag Tedlar bag, Mylar bag NR 5 L Mouth C NR 6 h
Koureas et al., 2021 (71) NR NR NR NR Inhale deeply and hold breath for 30 s, then exhale Tedlar bag NR 1 L Mouth NR NR NR
Lee et al., 2021 (23) NR NR Fast for at least 8 h and rest for at least 10 min in a preparation room for bronchoscopy with good ventilation before breath sampling In the morning between 9:00 and 11:00 Inhale gently and exhale for 5 min through a disposable mouthpiece Tedlar bag NR 200 mL Mouth NR NR NR
Li et al., 2021 (72) Y NR Did not to eat or drink (except water) for at least 30 min before breath collection and rest for 10 min NR NR Tedlar bag NR 500 mL NR NR NR NR
Liu et al., 2021 (73) NR NR Avoided a high-fat diet for dinner the night before sampling and fast, prohibition of alcohol, scented drink and smoking for 10–12 h. No toothpaste or mouthwash should be used at least 2 h prior to sampling. They should rinse mouth with clear water 3 times half an hour prior to sampling, and not take physical exercise at least 2 h prior to sampling In the morning from 07:00 to 09:00 before breakfast Alveolar Gas Collector Teflon bag Alveolar breath 10 L Mouth NR NR NR
Liu et al., 2021 (74) NR All Teflon bags should be washed with high purity nitrogen (99.999%) three times prior to sampling, and bags filled with nitrogen should be heated in a 50 ℃ chamber for one to two hours A high-fat diet for dinner the night before sampling should be avoided. And for both subjects and operators, fast, prohibition of alcohol, scented drink and smoking for 10–12 hours are needed. No toothpaste or mouthwash should be used at least 2 hours prior to sampling. Subjects should rinse their mouth with clear water 3 times half an hour prior to sampling. They should not take physical exercise at least 2 hours prior to sampling In the morning from 07:00 to 09:00 before breakfast NR Teflon bag Alveolar breath 10 L NR NR NR NR
Long et al., 2021 (40) NR NR Fasted for a minimum of 8 h and rest at least 20 min, healthy subjects were required to stop smoking and drinking at least 8 h before breath collection, while LC patients stopped smoking and drinking at least 3 d before sampling Before surgery Do not take nasal ventilation and exhale evenly Bio-VOC + Tedlar bag Alveolar breath 300 mL Mouth C −40 ℃ 7 d
Xia et al., 2021 (75) Y NR Rested for 1.0 h in a well-ventilated chamber NR Take a deep breath, exhale out the first third of breath, and then blow the remaining gas into the sample bag Tedlar bag NR 500 mL Mouth NR NR NR
Zou et al., 2021 (76) NR NR Had a 12h fasting and rinse out their mouth with distilled water before breath collection NR NR Self-made collection device + Tenax TA tube Alveolar breath 1 L NR C NR NR
Tsou et al., 2021 (15) Y Before collection, bags were flushed with nitrogen gas at least ten times to remove background VOCs associated with the bags Rinsed orally with water before breath collection and stayed in the same place for more than 30 min before collecting the gas NR Three-way connectors Aluminum bag Alveolar breath 1 L Mouth C At room temperature
(25 ℃)		 6 h
Gashimova et al., 2022 (16) NR Nitrogen was applied to clean the bags Fasted overnight. Active smokers did not smoke for at least 2.5 h before breath sampling. They had rested for 10 min in the room before collection NR Breathe deeply, hold the breath for 10 s, and breathe out calmly into the sampling bag until the bag was filled Tedlar bag NR NR NR C NR 6 h
Larracy et al., 2022 (17) Y NR Abstained from smoking for 4 h and drinking alcohol for 8 h prior to collection NR Breathe deeply and inhale An exhaled breath sampler+ Tenax TA sorbent tube Alveolar breath 10 L Mouth NR −20℃ NR
Wang et al., 2022 (7) Y On the night before breath collection, the Tedlar bags were baked at 60 ℃ for 3 h to fully release possible contaminants and continuously purged with high-purity nitrogen four times Fasted for at least 8 h and not to ingest spicy food, alcohol, or coffee the night before exhaled breath collection In the morning CO2-controlled manner Tedlar bag Alveolar breath 1 L Mouth C NR NR
Hao et al., 2023 (10) NR Tedlar bags were flushed with nitrogen to eliminate any contaminants before use Fasted for a minimum of 6 h in keeping with the standard protocol with no oral intake (including water) prior to their breath sample collection. Cleaned their mouth with water and freely breathed at least 30 min, and then sampling NR NR Tedlar bag NR NR NR NR NR NR
Temerdashev
et al., 2023 (11)		 Y Sampling bags pre-cleaned by flushing with nitrogen Fasted overnight and not smoke for 2.5 h before breath sampling. Rested for 10 min NR Breathe deeply, hold breath for 10 s and breathe Tedlar bag Mixed breath NR NR C NR 6 h
Li et al., 2017 (77) Y All Tedlar bags were washed with nitrogen three times prior to sampling Fasted overnight prior to sampling. Meanwhile, smokers were asked to stop smoking two hours prior to sampling. Rested for 3–5 minutes and rinsed their mouths with clear water 3–5 times NR Breath in deeply with their mouths, exhaling into sampling bags via a disposable mouth piece until the bags were filled Tedlar bag NR 2 L Mouth C NR 8 h
Chen et al., 2005 (78) NR NR NR NR NR Tedlar bag NR 2 L NR NR NR NR
Poli et al., 2005 (19) NR NR Rested for 60 min NR Perform a single slow vital capacity breath Bio-VOC + Teflon bulb Alveolar breath 150 mL NR NR NR NR
Mazzone et al., 2007 (79) Y NR NR NR Perform tidal breathing, inhale through nose and exhale through mouth A breath collection device NR NR Mouth NR NR NR
Dragonieri et al., 2009 (80) NR NR NR NR Inhale deeply and exhale Tedlar bag NR NR Mouth C NR NR
D'Amico et al., 2010 (81) NR NR No food or beverages were allowed since the night before the breath sampling In the early morning (7:00–10:00 am) NR Tedlar bag Alveolar breath 3 L NR NR NR NR
Mazzone et al., 2012 (82) NR NR NR NR Perform tidal breathing, inhale through nose and exhale through mouth NR NR NR Mouth NR NR NR
Santonico et al., 2012 (83) NR NR NR NR NR Tedlar bag Alveolar breath NR NR C NR Immediately
Wang et al., 2012 (84) Y NR Ate nothing and stop smoking for 12 hours NR Breathe normally through disposable mouthpiece and into the device Tedlar bag Alveolar breath 1 L Mouth NR NR NR
Broza et al., 2013 (85) NR NR NR During an interval of 1–3 days before the surgery; three weeks after the surgery In a controlled manner NR Alveolar breath NR Mouth NR NR 6 h
Bousamra et al., 2014 (86) NR NR NR NR NR Tedlar bag NR 1 L Mouth NR NR NR
Fu et al., 2014 (87) NR NR NR NR NR Tedlar bag Mixed breath 1 L NR NR NR NR
Zou et al., 2014 (88) NR NR Had a 12-hour fast and rinse out their mouth with distilled water before breath collection NR Breathe tidally through a disposal mouthpiece Tedlar bag Alveolar breath NR Mouth C NR Immediately
Capuano et al., 2015 (89) NR NR NR Before the bronchoscopic exam NR NR Mixed breath 3 L Mouth NR NR NR
Li et al., 2015 (90) Y NR NR NR NR Tedlar bag Mixed breath 1 L NR C NR NR
Schumer et al., 2015 (91) NR NR NR NR Take a single exhalation Tedlar bag NR NR NR NR NR NR
Tan et al., 2016 (92) NR NR Did not smoke or take any alcoholic beverage within 12 hours of the breath collection NR NR Vitagen container NR NR NR NR NR Immediately
Callol-Sanchez et al., 2017 (30) NR NR Fasting subjects had been rested for 1 h without smoking NR NR Bio-VOC Alveolar breath 1 L Mouth C NR 24 h
Kistenev et al., 2017 (31) NR NR Rinsed their mouths with running water without any special cleaning of the oral cavity Before eating or 2 h after Do some calm breaths Bio-VOC NR NR Mouth NR NR NR
Shlomi et al., 2017 (38) NR NR Did not to ingest coffee and food for at least one hour, alcohol for at least 12 hours and avoided smoking for at least half an hour prior to the breath collection NR Inhale to the level of total lung capacity and then exhale slowly GaSampler collection bag + Tenax tube Alveolar breath 750 mL Mouth NR 4 ℃ NR
Wang et al., 2018 (93) NR NR NR NR NR Tedlar bag Alveolar breath NR Mouth NR NR NR
Zuo et al., 2019 (94) Y The sampling bag was filled with high-purity nitrogen (99.9%), the filling amount did not exceed 80% (4 L) of the sampling bag volume Fasted for more than 8 hours, did not smoke for more than 12 hours before sampling, cleaned mouth with clear water before sampling, and did not brush teeth with toothpaste From 7:00 to 7:30 am Breathe calmly for 1 min, and inhale deeply Tedlar bag NR 2–4 L Mouth NR NR 2 h
Binson et al., 2021 (95) NR NR Fasted and did not to engage in any physical activity for two hours prior to breath sampling. Tobacco smoking, mouthwashes, toothpastes, and medications were not allowed NR Inhale deeply to total lung capacity and then exhale deeply Tedlar bag NR NR Mouth NR NR NR
Binson et al., 2021 (96) Y NR Fasted 2 hours before sampling, and did not smoke, use mouthwash, or use medications, and waited for 2 hours in a room NR Take a deep exhalation Tedlar bag NR 1 L Mouth NR NR NR
Binson et al., 2021 (14) Y NR Did not take food and water for a minimum of two hours before taking the breath sample and also smoking, mouth wash, toothpaste, medicines were not allowed NR Breathe deeply into the bag Tedlar bag NR 1 L Mouth NR NR NR
Binson et al., 2021 (97) Y Tedlar bags were cleaned with pure nitrogen twice before use Food and water were not given them for a minimum of two hours before taking the breath sample and also smoking, mouth wash, toothpaste, and medicines were prohibited. Rested for about 2 hours before sampling and then the mouth was washed 3–5 times with pure water NR Inhale deeply and exhale to the gas sampling bag through a BVF Tedlar bag NR 1 L Mouth NR NR 2 h
Chen et al., 2021 (22) Y NR Avoided high fat food and must not have taken any antioxidant supplements for at least 24 h before the test and observe 12 h of fast, did not brush teeth and gargled with plain tap water 15 min before the sample collection process NR NR Self-made device NR NR Mouth C NR NR
Marzorati et al., 2021 (34) NR NR Fasted within 8 hours before the test, avoided smoking the night before the test, not to eat aromatic food the day before the test, did not brush teeth after the last meal taken the evening before the test; to avoid perfumes or scented soap, in the twenty-four hours before the breath test NR NR Tedlar bag Alveolar breath NR NR C NR 24 h
Monedeiro et al., 2021 (36) NR The bags were filled and evacuated argon, then kept in an oven at 65 ℃ Avoided to eat, drink or smoke 2 h prior sample collection. Rest for 10 min NR NR Tedlar bag Mixed breath NR NR C NR 2–3 h
Zhao et al., 2021 (35) NR NR Did not eat breakfast and brush their teeth before collecting gas NR Alveolar gas collection system Teflon bag Alveolar breath 10 L NR NR NR NR
Rai et al., 2022 (28) NR NR NR NR Exhaled breath from the mouth Tedlar bag Mixed breath 1 L Mouth C NR NR
Wei et al., 2022 (8) NR Bags were repeatedly flushed with high-purity nitrogen three times before and after use NR NR Inhale through the nose, hold the nose, exhale the gas from mouth at one time FEP gas sampling bag Alveolar breath 1 L Mouth C In a incubator at a constant temperature 6 h
Smirnova et al., 2022 (6) NR NR Abstained from smoking, vaping, or drinking for at least 30 min before conducting the test NR Take a deep inhalation and exhale 150–300 mL of breath into the 0.5 L volume bag (Bag 1), then inflated the 1 L volume bag (Bag 2) using the rest of the exhaled breath Tedlar bag Alveolar breath 1 L NR NR At room temperature 2 h
Ding et al., 2023 (9) Y NR Fasted for at least 6 h before sample collection and were asked not to ingest spicy food, alcohol, or coffee the night before exhaled breath collection Before PET-CT scanning and the morning before surgery Perform a single deep nasal inhalation followed by complete exhalation via mouth into a bag Tedlar bag NR NR Mouth C NR 4 h

VOCs, volatile organic compounds; NR, not reported; Y, yes; C, collected; CO2, carbon dioxide; Bio-VOC, Bio-VOC breath sampler; BCA, breath collection apparatus; FEP, fluorinated ethylene propylene; LC, lung cancer; am, ante meridiem; pm, post meridiem; PET-CT, positron emission tomography-computed tomography; BVF, bacterial viral filter.

Process design

Through reading the 89 studies, we divided the collection of exhaled breath into three phases: before collection, during collection, and after collection. Before collection included assessments of the physiological condition of the patients, whether researchers had prepared a room for breath collection, and whether contamination detection was performed. During collection included the sampling time, breath collection containers, method of patient exhalation, breath volume, breath fraction selected, and environmental considerations. After collection included the storage of breath samples and VOCs stability. We summarized the three phases for each of the included studies and referred to the European Respiratory Society technical standard to propose a breath collection process (98).

For the assessment of the physiological condition of the patient, we recommend the patient to fast and refrain from smoking for 8–12 hours before breath collection, and to avoid brushing their teeth and taking non-essential medications on the morning of breath collection. We recommend that the researchers prepare a well-ventilated room for breath collection and clean the Tedlar bag by flushing with high-purity nitrogen before use. In terms of the selected breath fraction, we suggest that alveolar breath is the best choice, and the most common method used to capture the breath fraction is the carbon dioxide visual control. For the storage of breath samples, we recommend a 4 ℃ incubator. For assessing VOCs stability, we recommend that breath samples are analyzed within six hours (Figure 2).

Figure 2 The process of exhaled breath collection.

Quality assessment

The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included research papers (99). This assessment tool was used to assign a maximum of nine stars to each study. In this scale, each study was divided into three groups: selection of study groups, comparability between groups, and determination of outcomes. The greater the number of stars, the better the quality rating of the study (Appendices 2,3). Three independent reviewers (Y.H., Z.S., T.S.) carefully assessed the quality of included studies.

Results

Description of the included studies

Using the search strategy outlined previously, a total of 2,523 articles were acquired. Upon duplicate removal, 1,992 articles remained. Approximately 1,732 studies were excluded based on screening of the titles and abstracts, either due to lack of relevance or because they were patents. Consequently, a total of 260 studies remained, which were meticulously examined in their entirety. Of these, 171 studies were ultimately excluded as they failed to satisfy the specified inclusion criteria (Figure 1 and Appendix 4). Therefore, this systematic review included 89 studies (Table 1 and Appendix 5). In terms of the Newcastle-Ottawa Scale score, 31 studies were awarded seven stars, and 22 studies were awarded more than seven stars. The methods used to collect the exhaled breath in these studies are shown in Table 1.

We analyzed the data of 6,409 patients with lung cancer from 19 countries. Of the 89 included studies, 30 were conducted in China, 11 in the USA, 7 in Italy, 6 in Poland, 5 in Russia, 4 in Austria, 4 in India (from the same group), 3 in Israel, 3 in Germany, 3 in Korea, 2 in Greece (from the same group), and 2 in Japan. The rest were conducted in Portugal, Belgium, Morocco, Canada, the Netherlands, Malaysia, and Spain. The number of patients with lung cancer in these studies ranged from 6 to 389. Fifty-five studies compared patients with lung cancer to a healthy control population, while 34 studies compared patients with lung cancer to patients with other conditions affecting the same organ. The studies generally included patients at different stages of tumor progression, although 36 studies did not report the tumor stage. The physiological conditions of the patients before breath collection were described in 57 studies, environmental considerations in 41, type of breath collection container in 86, selected breath fraction in 56, storage conditions of breath samples in 15, and VOCs stability in 41.

Before breath collection

In 29 studies, a separate room was prepared for breath collection. Breath collection container contamination was recorded in 32 studies, 26 of which reported cleaning of the sampling containers [Tedlar bag, Mylar bag, aluminum bag, Teflon bag, fluorinated ethylene propylene (FEP) gas sampling bag, or Bio-VOC breath sampler] by nitrogen flushing. Additionally, six studies used argon gas to clean the sampling bags (Tedlar bags) multiple times. Furthermore, 11 studies mentioned that the sampling bags were heated before use, with the heating temperature ranging from 45 to 95 ℃ and the heating times ranging from 1 to 12 hours. Fifty-seven studies described the preparation of participants before breath collection, with 45 studies requiring participants to fast for a duration ranging from 0.5 to 12 hours, 28 studies requiring participants to avoid smoking, and five studies requiring participants not to use medications. Sixteen studies asked the participants to take a rest prior to sampling, and 11 studies instructed the participants not to use toothpaste or mouthwash before breath collection to minimize the negative effects of exogenous VOCs.

During breath collection

Only 19 studies reported the sampling time, with 10 studies specifying a sampling time between 7:00 and 11:30 in the morning. The other nine studies did not have detailed time descriptions. The most commonly used breath container for collecting exhaled VOCs was the Tedlar bag, which was used in 58 of the 89 studies. Four studies used portable breath collection apparatus and three studies used Teflon bag. Two studies used self-made collection device. Two studies used both the Bio-VOC breath sampler and Tedlar bag, and one study used both the Bio-VOC breath sampler and Teflon bulb. One study compared the Tedlar bag with the Mylar bag. Additionally, three studies utilized the Bio-VOC breath sampler, two studies used the FEP gas sampling bag, and two studies used the analytic barrier bag. Four studies each used the Mylar bag, aluminum bag, Vitagen container and Devex bag. Fifty-one studies mentioned that the patients exhaled breath from the mouth. In terms of the breath fraction sampled, 43 studies collected alveolar breath, nine of which used a carbon dioxide controlled method and two of which used an alveolar gas collection system. Additionally, 13 studies selected mixed expiratory breath. However, 33 studies did not specify the breath fraction selected. Twenty-three studies selected one litre as the volume of breath, and 41 studies collected ambient air.

Measures after breath collection

In 74 of the 89 studies, the specific storage conditions of the samples were not mentioned. Among the studies that did provide storage information, five reported storing the breath samples at room temperature, four at 4 ℃, two at −40 ℃, one at −15 ℃, one at −20 ℃, one in an opaque box and one in an incubator at a constant temperature. Additionally, the timing between sampling varied among the studies. In 35 studies, the storage time ranged from 2 hours to 7 days after breath collection. Of these, 13 studies analyzed the samples within 6 hours, which was the most frequently reported storage time. Six studies analyzed the samples within 2 hours. Two studies reported that the breath samples were kept at −40 ℃ until analysis (within 7 days). Six studies analyzed the breath samples immediately after collection.

Discussion

Key findings

In this review, we evaluated the methods used for exhaled breath collection and the heterogeneity among published studies in the three phases of breath collection. The main findings of this study were as follows: (I) preparation before sample collection, breath collection containers, the fraction of breath selected, the storage conditions of the samples, and the stability of VOCs differed between studies; and (II) expiratory flow rate and breath hold may be important for breath collection.

Preparations before sample collection

The composition of VOCs in exhaled breath is complex and is influenced by several factors, including smoking (100), diet (101), comorbidities (102), pharmacological treatment (103), exercise (104,105), and atmospheric background (98). Efforts to reduce the impact of these factors on breath analysis include prohibition of exercise, smoking, food consumption, and beverage intake 2–12 hours before breath collection (23,62,73,74). However, whether these factors improve the reliability of breath analysis remains to be investigated. The stability of most compounds in humid air is up to 10% lower than in a dry environment (106), so a moderately ventilated environment is suitable for breath collection.

Breath collection containers

Polymer bags are commonly used as breath collection containers. Tedlar bags are the most frequently utilized polymer bags, especially for collecting exhaled VOCs. This is due to their affordability, inertness, and relatively good durability. Mochalski et al. showed that Tedlar bags demonstrated superior performance to Kynar bags and FlexFilm sample bags in terms of analyte stability (106). It is suggested that Tedlar bags are suitable for human breath storage. For instance, Steeghs et al. showed that the recovery of sampled gas concentrations over time was >90% at 52 hours after filling (107). Both new bags and bags that have previously been used to store breath samples can exhibit a certain level of contamination. Phenol is likely contaminant of Tedlar bags (61). Therefore, pre-cleaning is important, and an appropriate cleaning protocol and handling technique should be applied. Han et al. showed that VOCs previously adsorbed by the Tedlar bag can be released after filling pure nitrogen into the Tedlar bag (108).

Bio-VOC samplers, breath collection apparatus, and glass vials have also been utilized for breath collection (109). The Bio-VOC breath sampler has an open end that permits air to be expelled during exhalation. This allows for the collection of alveolar air, which is less affected by environmental pollution and is therefore more likely as representative of the condition of the lungs (110). However, due to the limitations on the sampling capacity, it is recommended to use the Bio-VOC breath sampler exclusively for detecting VOCs present at high concentrations (111). As a commercial sampling device, the Bio-VOC sampler may have high-cost problems, which may limit its application in some research or clinical settings.

Fraction of breath selected

Different breath collection results may be obtained depending on the breath fraction selected. The main fractions are alveolar (end-tidal) breath and mixed expiratory breath.

Mixed expiratory breath is considered as the simplest breath fraction to obtain as it acquires all phases of exhaled air. However, mixed expiratory breath may not provide the best quality breath samples due to the greater abundance of environmental, mouth, and nose contaminants (4).

The most commonly selected breath fraction among the studies included in this review was alveolar breath. Alveolar breath contains significant levels of naturally occurring VOCs while being relatively free from impurities (4). Enriched alveolar breath can be obtained by expired carbon dioxide triggers or by discarding the first part of the exhaled breath, which corresponds to the dead space air (7,25,66). The most commonly used device to collect alveolar breath is carbon dioxide visual control, which can monitor the carbon dioxide concentration during exhalation. This method is effective, but it is cumbersome, time-consuming, and not suitable for routine diagnostic treatment. Besides, alveolar breath can be captured using the three-way valve and flow meter (84,88).

Expiratory flow rate and breath hold

VOCs levels are affected by exhalation parameters, such as expiratory flow rate and breath hold (112). However, the specific expiratory flow rates were not mentioned in the studies included in this review. Only one study reported a low flow rate, which was achieved by slowly expelling the air and thereby increasing the efficiency (95). It has been reported that the flow rate of the breath only alters the sensor array outputs of control subjects and not those of patients with pulmonary diseases (112). Moreover, many VOCs have shown higher concentrations in samples collected at lower breathing flow rates than at higher breathing flow rates (113). Thus far, few studies have evaluated the influence of expiratory flow rate on VOCs. Moreover, whether the expiratory flow rate needs to be restricted during breath collection remains to be clarified.

VOCs stability

The most commonly used polymer bags designed for the transport and storage of breath samples for breath composition analysis are Tedlar bags. Most studies have reported relatively good stability of compounds when stored in Tedlar bags for at least six hours. Ghimenti et al. found that acetone, 2-propanol and hexanal showed a 20% loss within 6 h for the Tedlar bag by comparing three different types of sampling bags (114). Beauchamp et al. showed that the majority of compounds in exhaled breath stored in the Tedlar bag remained relatively stable for up to 10 hours with acceptable percentage recovery (>80%) (115). By comparing the storage capabilities of three types of polymer sampling bag (Tedlar, Kynar, and FlexFilm), Mochalski et al. recommended analyzing breath samples in Tedlar bags within six hours (106). Furthermore, Li et al. showed that the degradation of compounds in the breath was reduced and the appropriate storage time was prolonged to two hours if the breath samples were stored at cold temperatures (4 ℃) (116). In Mochalski et al.’ study, fourteen compounds were found to be stable during the first four weeks of storage at cold temperatures (−80 ℃) (117).

The capacity and sensitivity of breath testing

Breath testing, as an emerging method for lung cancer detecting, has the advantages of being non-invasive and easy to operate, and it is currently widely concerned in the field of lung cancer. Numerous studies used GC-MS or electronic nose to detect the profile of exhaled VOCs in lung cancer and controls, with the sensitivity ranging from 76% to 100% and the specificity ranging from 80% to 96% in lung cancer diagnosis (11,14,41,63,66,67,77,97). Although it is generally accepted that breath testing may play a role in early lung cancer diagnosis, there are not many studies investigating the effect of tumor stage on the breath test performance and the results of these studies are often inconsistent (32,62,70,84,88,91). Future studies should aim to clarify the specific impact of tumor stage and other factors, such as the association of histology and molecular subtype with the diagnostic accuracy of breath testing (118).

Strengths and limitations

This review provides an overview of the methods that have been used to collect exhaled breath for lung cancer screening and diagnosis, as well as proposing a complete breath collection process. However, there are some limitations in this study that should be considered. First, only studies published in the English language were included. The exclusion of non-English-language studies means that some breath collection methods may have been missed. Second, we did not distinguish between studies that screened for lung cancer by exhaled breath analysis and those that actually diagnosed lung cancer, which may have influenced the summary of the breath collection methods. Additionally, this review did not categorize the breath collection methods based on their respective breath analysis techniques, such as GC-MS and electronic noses, which may be a source of heterogeneity among the collection methods. Future studies should formulate breath collection methods according to different analytical techniques.

Conclusions

There is a great need for further standardization of exhaled breath collection procedures to substantiate the usefulness of VOCs analysis in clinical medicine, including lung cancer screening and diagnosis. This review suggests that the breath collection process should consider several factors, including the environmental conditions, physiological condition of the patient, type of breath container, contamination, breath fraction selected, sample storage conditions, and VOCs stability. Therefore, expanding upon previous studies, we propose a breath collection process: preparations of investigators and patients before breath collection, practices of investigators and patients during breath collection, storage of breath samples and VOCs stability after breath collection. The complete process of exhaled breath collection is shown in Figure 2, which may be a beneficial reference for clinical practice.

Acknowledgments

We would like to thank TopEdit for their help in polishing our paper.

Funding: This study was supported by 2022 Jiangsu Provincial Science and Technology Program Special Funds (Key R&D Program for Social Development) (Grant No. BE2022775).

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1001/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1001/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1001/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
  2. Cao M, Chen W. Epidemiology of lung cancer in China. Thorac Cancer 2019;10:3-7. [Crossref] [PubMed]
  3. Foley RW, Nassour V, Oliver HC, et al. Chest X-ray in suspected lung cancer is harmful. Eur Radiol 2021;31:6269-74. [Crossref] [PubMed]
  4. Lawal O, Ahmed WM, Nijsen TME, et al. Exhaled breath analysis: a review of 'breath-taking' methods for off-line analysis. Metabolomics 2017;13:110. [Crossref] [PubMed]
  5. McWilliams A, Shaipanich T, Lam S. Fluorescence and navigational bronchoscopy. Thorac Surg Clin 2013;23:153-61. [Crossref] [PubMed]
  6. Smirnova E, Mallow C, Muschelli J, et al. Predictive performance of selected breath volatile organic carbon compounds in stage 1 lung cancer. Transl Lung Cancer Res 2022;11:1009-18. [Crossref] [PubMed]
  7. Wang P, Huang Q, Meng S, et al. Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study. EClinicalMedicine 2022;47:101384. [Crossref] [PubMed]
  8. Wei X, Li Q, Wu Y, et al. Determination of breath isoprene in 109 suspected lung cancer patients using cavity ringdown spectroscopy. J Innovative Opt Health Sci 2022;15:225029.
  9. Ding X, Lin G, Wang P, et al. Diagnosis of primary lung cancer and benign pulmonary nodules: a comparison of the breath test and 18F-FDG PET-CT. Front Oncol 2023;13:1204435. [Crossref] [PubMed]
  10. Hao QL, Wang SW, Yu LQ, et al. Immobilization of zeolitic imidazolate framework-90 onto modified stainless steel wire via covalent bonding for solid-phase microextraction of biomarkers in exhalation of lung cancer patients. Sep Sci Plus 2023;6:2300026.
  11. Temerdashev AZ, Gashimova EM, Porkhanov VA, et al. Non-Invasive Lung Cancer Diagnostics through Metabolites in Exhaled Breath: Influence of the Disease Variability and Comorbidities. Metabolites 2023;13:203. [Crossref] [PubMed]
  12. Phillips M. Method for the collection and assay of volatile organic compounds in breath. Anal Biochem 1997;247:272-8. [Crossref] [PubMed]
  13. Gordon SM, Szidon JP, Krotoszynski BK, et al. Volatile organic compounds in exhaled air from patients with lung cancer. Clin Chem 1985;31:1278-82.
  14. Binson VA, Subramoniam M, Mathew L. Discrimination of COPD and lung cancer from controls through breath analysis using a self-developed e-nose. J Breath Res 2021;
  15. Tsou PH, Lin ZL, Pan YC, et al. Exploring Volatile Organic Compounds in Breath for High-Accuracy Prediction of Lung Cancer. Cancers (Basel) 2021;13:1431. [Crossref] [PubMed]
  16. Gashimova E, Temerdashev A, Porkhanov V, et al. Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy. ACS Omega 2022;7:42613-28. [Crossref] [PubMed]
  17. Larracy R, Phinyomark A, Scheme E. Infrared cavity ring-down spectroscopy for detecting non-small cell lung cancer in exhaled breath. J Breath Res 2022;
  18. Hanna GB, Boshier PR, Markar SR, et al. Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis. JAMA Oncol 2019;5:e182815. [Crossref] [PubMed]
  19. Poli D, Carbognani P, Corradi M, et al. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respir Res 2005;6:71. [Crossref] [PubMed]
  20. Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 2009;9:348. [Crossref] [PubMed]
  21. Saidi T, Moufid M, de Jesus Beleno-Saenz K, et al. Non-invasive prediction of lung cancer histological types through exhaled breath analysis by UV-irradiated electronic nose and GC/QTOF/MS. Sensor Actuat B-Chem 2020;311:127932.
  22. Chen X, Muhammad KG, Madeeha C, et al. Calculated indices of volatile organic compounds (VOCs) in exhalation for lung cancer screening and early detection. Lung Cancer 2021;154:197-205. [Crossref] [PubMed]
  23. Lee JM, Choi EJ, Chung JH, et al. A DNA-derived phage nose using machine learning and artificial neural processing for diagnosing lung cancer. Biosens Bioelectron 2021;194:113567. [Crossref] [PubMed]
  24. Peng G, Tisch U, Adams O, et al. Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat Nanotechnol 2009;4:669-73. [Crossref] [PubMed]
  25. Chang JE, Lee DS, Ban SW, et al. Analysis of volatile organic compounds in exhaled breath for lung cancer diagnosis using a sensor system. Sensor Actuat B-Chem 2018;255:800-7.
  26. Huang CH, Zeng C, Wang YC, et al. A Study of Diagnostic Accuracy Using a Chemical Sensor Array and a Machine Learning Technique to Detect Lung Cancer. Sensors (Basel) 2018;18:2845. [Crossref] [PubMed]
  27. Gashimova E, Osipova A, Temerdashev A, et al. Study of confounding factors influence on lung cancer diagnostics effectiveness using gas chromatography-mass spectrometry analysis of exhaled breath. Biomark Med 2021;15:821-9. [Crossref] [PubMed]
  28. Rai SN, Das S, Pan J, et al. Multigroup prediction in lung cancer patients and comparative controls using signature of volatile organic compounds in breath samples. PLoS One 2022;17:e0277431. [Crossref] [PubMed]
  29. Poli D, Goldoni M, Corradi M, et al. Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878:2643-51. [Crossref] [PubMed]
  30. Callol-Sanchez L, Munoz-Lucas MA, Gomez-Martin O, et al. Observation of nonanoic acid and aldehydes in exhaled breath of patients with lung cancer. J Breath Res 2017;11:026004. [Crossref] [PubMed]
  31. Kistenev YV, Borisov AV, Kuzmin DA, et al. Exhaled air analysis using wideband wave number tuning range infrared laser photoacoustic spectroscopy. J Biomed Opt 2017;22:17002. [Crossref] [PubMed]
  32. Phillips M, Altorki N, Austin JH, et al. Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomark 2007;3:95-109. [Crossref] [PubMed]
  33. Phillips M, Bauer TL, Cataneo RN, et al. Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening. PLoS One 2015;10:e0142484. [Crossref] [PubMed]
  34. Marzorati D, Mainardi L, Sedda G, et al. MOS Sensors Array for the Discrimination of Lung Cancer and At-Risk Subjects with Exhaled Breath Analysis. Chemosensors 2021;9:209.
  35. Zhao L, Qian J, Tian F, et al. A Weighted Discriminative Extreme Learning Machine Design for Lung Cancer Detection by an Electronic Nose System. IEEE Trans Instrum Meas 2021;70:2509709.
  36. Monedeiro F, Monedeiro-Milanowski M, Ratiu IA, et al. Needle Trap Device-GC-MS for Characterization of Lung Diseases Based on Breath VOC Profiles. Molecules 2021;26:1789. [Crossref] [PubMed]
  37. Gashimova E, Temerdashev A, Porkhanov V, et al. Investigation of different approaches for exhaled breath and tumor tissue analyses to identify lung cancer biomarkers. Heliyon 2020;6:e04224. [Crossref] [PubMed]
  38. Shlomi D, Abud M, Liran O, et al. Detection of Lung Cancer and EGFR Mutation by Electronic Nose System. J Thorac Oncol 2017;12:1544-51. [Crossref] [PubMed]
  39. Li W, Dai W, Liu M, et al. VOC biomarkers identification and predictive model construction for lung cancer based on exhaled breath analysis: research protocol for an exploratory study. BMJ Open 2019;9:e028448. [Crossref] [PubMed]
  40. Long Y, Wang C, Wang T, et al. High performance exhaled breath biomarkers for diagnosis of lung cancer and potential biomarkers for classification of lung cancer. J Breath Res 2021;15:016017. [Crossref] [PubMed]
  41. Phillips M, Gleeson K, Hughes JM, et al. Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 1999;353:1930-3. [Crossref] [PubMed]
  42. Yu H, Xu L, Wang P. Solid phase microextraction for analysis of alkanes and aromatic hydrocarbons in human breath. J Chromatogr B Analyt Technol Biomed Life Sci 2005;826:69-74. [Crossref] [PubMed]
  43. Wehinger A, Schmid A, Mechtcheriakov S, et al. Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas. Int J Mass Spectrom 2007;265:49-59.
  44. Phillips M, Altorki N, Austin JH, et al. Detection of lung cancer using weighted digital analysis of breath biomarkers. Clin Chim Acta 2008;393:76-84. [Crossref] [PubMed]
  45. Gaspar EM, Lucena AF, Duro da Costa J, et al. Organic metabolites in exhaled human breath--a multivariate approach for identification of biomarkers in lung disorders. J Chromatogr A 2009;1216:2749-56. [Crossref] [PubMed]
  46. Ligor M, Ligor T, Bajtarevic A, et al. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry. Clin Chem Lab Med 2009;47:550-60. [Crossref] [PubMed]
  47. Westhoff M, Litterst P, Freitag L, et al. Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study. Thorax 2009;64:744-8. [Crossref] [PubMed]
  48. Fuchs P, Loeseken C, Schubert JK, et al. Breath gas aldehydes as biomarkers of lung cancer. Int J Cancer 2010;126:2663-70. [Crossref] [PubMed]
  49. Kischkel S, Miekisch W, Sawacki A, et al. Breath biomarkers for lung cancer detection and assessment of smoking related effects - confounding variables, influence of normalization and statistical algorithms. Clin Chim Acta 2010;411:1637-44. [Crossref] [PubMed]
  50. Song G, Qin T, Liu H, et al. Quantitative breath analysis of volatile organic compounds of lung cancer patients. Lung Cancer 2010;67:227-31. [Crossref] [PubMed]
  51. Tran VH, Chan HP, Thurston M, et al. Breath Analysis of Lung Cancer Patients Using an Electronic Nose Detection System. IEEE Sens J 2010;10:1514-8.
  52. Buszewski B, Ulanowska A, Kowalkowski T, et al. Investigation of lung cancer biomarkers by hyphenated separation techniques and chemometrics. Clin Chem Lab Med 2011;50:573-81. [Crossref] [PubMed]
  53. Rudnicka J, Kowalkowski T, Ligor T, et al. Determination of volatile organic compounds as biomarkers of lung cancer by SPME-GC-TOF/MS and chemometrics. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:3360-6. [Crossref] [PubMed]
  54. Ulanowska A, Kowalkowski T, Trawińska E, et al. The application of statistical methods using VOCs to identify patients with lung cancer. J Breath Res 2011;5:046008. [Crossref] [PubMed]
  55. Buszewski B, Ligor T, Jezierski T, et al. Identification of volatile lung cancer markers by gas chromatography-mass spectrometry: comparison with discrimination by canines. Anal Bioanal Chem 2012;404:141-6. [Crossref] [PubMed]
  56. Filipiak W, Filipiak A, Sponring A, et al. Comparative analyses of volatile organic compounds (VOCs) from patients, tumors and transformed cell lines for the validation of lung cancer-derived breath markers. J Breath Res 2014;8:027111. [Crossref] [PubMed]
  57. Gi BH, Jeung S, Ok LJ, et al. Exhaled Breath Analysis System based on Electronic Nose Techniques Applicable to Lung Diseases. Hanyang Med Rev 2014;34:125-9.
  58. Ma H, Li X, Chen J, et al. Analysis of human breath samples of lung cancer patients and healthy controls with solid-phase microextraction (SPME) and flow-modulated comprehensive two-dimensional gas chromatography (GC x GC). Anal Methods 2014;6:6841-9.
  59. Ligor T, Pater Ł, Buszewski B. Application of an artificial neural network model for selection of potential lung cancer biomarkers. J Breath Res 2015;9:027106. [Crossref] [PubMed]
  60. Gasparri R, Santonico M, Valentini C, et al. Volatile signature for the early diagnosis of lung cancer. J Breath Res 2016;10:016007. [Crossref] [PubMed]
  61. Itoh T, Miwa T, Tsuruta A, et al. Development of an Exhaled Breath Monitoring System with Semiconductive Gas Sensors, a Gas Condenser Unit, and Gas Chromatograph Columns. Sensors (Basel) 2016;16:1891. [Crossref] [PubMed]
  62. Sakumura Y, Koyama Y, Tokutake H, et al. Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm. Sensors (Basel) 2017;17:287. [Crossref] [PubMed]
  63. Cai X, Chen L, Kang T, et al. A Prediction Model with a Combination of Variables for Diagnosis of Lung Cancer. Med Sci Monit 2017;23:5620-9. [Crossref] [PubMed]
  64. Yu LQ, Wang LY, Su FH, et al. A gate-opening controlled metal-organic framework for selective solid-phase microextraction of aldehydes from exhaled breath of lung cancer patients. Mikrochim Acta 2018;185:307. [Crossref] [PubMed]
  65. Pesesse R, Stefanuto PH, Schleich F, et al. Multimodal chemometric approach for the analysis of human exhaled breath in lung cancer patients by TD-GC × GC-TOFMS. J Chromatogr B Analyt Technol Biomed Life Sci 2019;1114-1115:146-53. [Crossref] [PubMed]
  66. Rudnicka J, Kowalkowski T, Buszewski B. Searching for selected VOCs in human breath samples as potential markers of lung cancer. Lung Cancer 2019;135:123-9. [Crossref] [PubMed]
  67. Chen Q, Chen Z, Liu D, et al. Constructing an E-Nose Using Metal-Ion-Induced Assembly of Graphene Oxide for Diagnosis of Lung Cancer via Exhaled Breath. ACS Appl Mater Interfaces 2020;12:17713-24. [Crossref] [PubMed]
  68. Koureas M, Kirgou P, Amoutzias G, et al. Target Analysis of Volatile Organic Compounds in Exhaled Breath for Lung Cancer Discrimination from Other Pulmonary Diseases and Healthy Persons. Metabolites 2020;10:317. [Crossref] [PubMed]
  69. Li W, Jia Z, Xie D, et al. Recognizing lung cancer using a homemade e-nose: A comprehensive study. Comput Biol Med 2020;120:103706. [Crossref] [PubMed]
  70. Chen K, Liu L, Nie B, et al. Recognizing lung cancer and stages using a self-developed electronic nose system. Comput Biol Med 2021;131:104294. [Crossref] [PubMed]
  71. Koureas M, Kalompatsios D, Amoutzias GD, et al. Comparison of Targeted and Untargeted Approaches in Breath Analysis for the Discrimination of Lung Cancer from Benign Pulmonary Diseases and Healthy Persons. Molecules 2021;26:2609. [Crossref] [PubMed]
  72. Li Z, Li Y, Zhan L, et al. Point-of-Care Test Paper for Exhaled Breath Aldehyde Analysis via Mass Spectrometry. Anal Chem 2021;93:9158-65. [Crossref] [PubMed]
  73. Liu B, Yu H, Zeng X, et al. Lung cancer detection via breath by electronic nose enhanced with a sparse group feature selection approach. Sensor Actuat B-Chem 2021;339:129896.
  74. Liu B, Zeng X, Yu H, et al. Sparse Unidirectional Domain Adaptation Algorithm for Instrumental Variation Correction of Electronic Nose Applied to Lung Cancer Detection. IEEE Sens J 2021;21:17025-39.
  75. Xia Z, Li D, Deng W. Identification and Detection of Volatile Aldehydes as Lung Cancer Biomarkers by Vapor Generation Combined with Paper-Based Thin-Film Microextraction. Anal Chem 2021;93:4924-31. [Crossref] [PubMed]
  76. Zou Y, Wang Y, Jiang Z, et al. Breath profile as composite biomarkers for lung cancer diagnosis. Lung Cancer 2021;154:206-13. [Crossref] [PubMed]
  77. Li W, Liu H, Xie D, et al. Lung Cancer Screening Based on Type-different Sensor Arrays. Sci Rep 2017;7:1969. [Crossref] [PubMed]
  78. Chen X, Cao MF, Li Y, et al. A study of an electronic nose for detection of lung cancer based on a virtual SAW gas sensors array and imaging recognition method. Meas Sci Technol 2005;16:1535-46.
  79. Mazzone PJ, Hammel J, Dweik R, et al. Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax 2007;62:565-8. [Crossref] [PubMed]
  80. Dragonieri S, Annema JT, Schot R, et al. An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 2009;64:166-70. [Crossref] [PubMed]
  81. D'Amico A, Pennazza G, Santonico M, et al. An investigation on electronic nose diagnosis of lung cancer. Lung Cancer 2010;68:170-6. [Crossref] [PubMed]
  82. Mazzone PJ, Wang XF, Xu Y, et al. Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer. J Thorac Oncol 2012;7:137-42. [Crossref] [PubMed]
  83. Santonico M, Lucantoni G, Pennazza G, et al. In situ detection of lung cancer volatile fingerprints using bronchoscopic air-sampling. Lung Cancer 2012;77:46-50. [Crossref] [PubMed]
  84. Wang Y, Hu Y, Wang D, et al. The analysis of volatile organic compounds biomarkers for lung cancer in exhaled breath, tissues and cell lines. Cancer Biomark 2012;11:129-37. [Crossref] [PubMed]
  85. Broza YY, Kremer R, Tisch U, et al. A nanomaterial-based breath test for short-term follow-up after lung tumor resection. Nanomedicine 2013;9:15-21. [Crossref] [PubMed]
  86. Bousamra M 2nd, Schumer E, Li M, et al. Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease. J Thorac Cardiovasc Surg 2014;148:1074-80; discussion 1080-1. [Crossref] [PubMed]
  87. Fu XA, Li M, Knipp RJ, et al. Noninvasive detection of lung cancer using exhaled breath. Cancer Med 2014;3:174-81. [Crossref] [PubMed]
  88. Zou Y, Zhang X, Chen X, et al. Optimization of volatile markers of lung cancer to exclude interferences of non-malignant disease. Cancer Biomark 2014;14:371-9. [Crossref] [PubMed]
  89. Capuano R, Santonico M, Pennazza G, et al. The lung cancer breath signature: a comparative analysis of exhaled breath and air sampled from inside the lungs. Sci Rep 2015;5:16491. [Crossref] [PubMed]
  90. Li M, Yang D, Brock G, et al. Breath carbonyl compounds as biomarkers of lung cancer. Lung Cancer 2015;90:92-7. [Crossref] [PubMed]
  91. Schumer EM, Trivedi JR, van Berkel V, et al. High sensitivity for lung cancer detection using analysis of exhaled carbonyl compounds. J Thorac Cardiovasc Surg 2015;150:1517-22; discussion 1522-4. [Crossref] [PubMed]
  92. Tan JL, Yong ZX, Liam CK. Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer. J Thorac Dis 2016;8:2772-83. [Crossref] [PubMed]
  93. Wang M, Sheng J, Wu Q, et al. Confounding effect of benign pulmonary diseases in selecting volatile organic compounds as markers of lung cancer. J Breath Res 2018;12:046013. [Crossref] [PubMed]
  94. Zuo W, Bai W, Gan X, et al. Detection of Lung Cancer by Analysis of Exhaled Gas Utilizing Extractive Electrospray Ionization-Mass Spectroscopy. J Biomed Nanotechnol 2019;15:633-46. [Crossref] [PubMed]
  95. Binson VA, Subramoniam M, Mathew L. Noninvasive detection of COPD and Lung Cancer through breath analysis using MOS Sensor array based e-nose. Expert Rev Mol Diagn 2021;21:1223-33. [Crossref] [PubMed]
  96. Binson VA, Subramoniam M, Mathew L. Detection of COPD and Lung Cancer with electronic nose using ensemble learning methods. Clin Chim Acta 2021;523:231-8. [Crossref] [PubMed]
  97. Binson VA, Subramoniam M, Sunny Y, et al. Prediction of Pulmonary Diseases With Electronic Nose Using SVM and XGBoost. IEEE Sens J 2021;21:20886-95.
  98. Horváth I, Barnes PJ, Loukides S, et al. A European Respiratory Society technical standard: exhaled biomarkers in lung disease. Eur Respir J 2017;49:1600965. [Crossref] [PubMed]
  99. De Cassai A, Boscolo A, Zarantonello F, et al. Enhancing study quality assessment: an in-depth review of risk of bias tools for meta-analysis-a comprehensive guide for anesthesiologists. J Anesth Analg Crit Care 2023;3:44. [Crossref] [PubMed]
  100. Pauwels CGGM, Hintzen KFH, Talhout R, et al. Smoking regular and low-nicotine cigarettes results in comparable levels of volatile organic compounds in blood and exhaled breath. J Breath Res 2020;15:016010. [Crossref] [PubMed]
  101. Krilaviciute A, Leja M, Kopp-Schneider A, et al. Associations of diet and lifestyle factors with common volatile organic compounds in exhaled breath of average-risk individuals. J Breath Res 2019;13:026006. [Crossref] [PubMed]
  102. Gashimova E, Temerdashev A, Perunov D, et al. Diagnosis of Lung Cancer Through Exhaled Breath: A Comprehensive Study. Mol Diagn Ther 2024;28:847-60. [Crossref] [PubMed]
  103. Lim CS, Rani FA, Tan LE. Response of exhaled nitric oxide to inhaled corticosteroids in patients with stable COPD: A systematic review and meta-analysis. Clin Respir J 2018;12:218-26. [Crossref] [PubMed]
  104. Heaney LM, Kang S, Turner MA, et al. The Impact of a Graded Maximal Exercise Protocol on Exhaled Volatile Organic Compounds: A Pilot Study. Molecules 2022;27:370. [Crossref] [PubMed]
  105. Dragonieri S, Marco MD, Ahroud M, et al. Electronic nose based analysis of exhaled volatile organic compounds spectrum reveals asthmatic shifts and consistency in controls post-exercise and spirometry. J Breath Res 2024;
  106. Mochalski P, King J, Unterkofler K, et al. Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags. Analyst 2013;138:1405-18. [Crossref] [PubMed]
  107. Steeghs MM, Cristescu SM, Harren FJ. The suitability of Tedlar bags for breath sampling in medical diagnostic research. Physiol Meas 2007;28:73-84. [Crossref] [PubMed]
  108. Han F, Zhong H, Li T, et al. Storage Stability of Volatile Organic Compounds from Petrochemical Plant of China in Different Sample Bags. J Anal Methods Chem 2020;2020:9842569. [Crossref] [PubMed]
  109. Rattray NJ, Hamrang Z, Trivedi DK, et al. Taking your breath away: metabolomics breathes life in to personalized medicine. Trends Biotechnol 2014;32:538-48. [Crossref] [PubMed]
  110. Jia Z, Thavasi V, Venkatesan T, et al. Breath Analysis for Lung Cancer Early Detection-A Clinical Study. Metabolites 2023;13:1197. [Crossref] [PubMed]
  111. Kwak J, Fan M, Harshman SW, et al. Evaluation of Bio-VOC Sampler for Analysis of Volatile Organic Compounds in Exhaled Breath. Metabolites 2014;4:879-88. [Crossref] [PubMed]
  112. Bikov A, Hernadi M, Korosi BZ, et al. Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer. BMC Pulm Med 2014;14:202. [Crossref] [PubMed]
  113. Thekedar B, Oeh U, Szymczak W, et al. Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations. J Breath Res 2011;5:016001. [Crossref] [PubMed]
  114. Ghimenti S, Lomonaco T, Bellagambi FG, et al. Comparison of sampling bags for the analysis of volatile organic compounds in breath. J Breath Res 2015;9:047110. [Crossref] [PubMed]
  115. Beauchamp J, Herbig J, Gutmann R, et al. On the use of Tedlar® bags for breath-gas sampling and analysis. J Breath Res 2008;2:046001. [Crossref] [PubMed]
  116. Li Q, Fu X, Xu K, et al. A stability study of carbonyl compounds in Tedlar bags by a fabricated MEMS microreactor approach. Microchem J 2021;160:105611.
  117. Mochalski P, Mayhew CA. Stability of selected exhaled breath volatiles stored in Tenax(®)TA adsorbent tubes at -80 °C. J Breath Res 2024;
  118. Zhang J, He X, Guo X, et al. Identification potential biomarkers for diagnosis, and progress of breast cancer by using high-pressure photon ionization time-of-flight mass spectrometry. Anal Chim Acta 2024;1320:342883. [Crossref] [PubMed]
Cite this article as: He Y, Su Z, Sha T, Yu X, Guo H, Tao Y, Liao L, Zhang Y, Lu G, Lu G, Gong W. Collection methods of exhaled volatile organic compounds for lung cancer screening and diagnosis: a systematic review. J Thorac Dis 2024;16(11):7978-7998. doi: 10.21037/jtd-24-1001

Article Options

Download Citation

Share