Effect of smoking on the diagnostic results and complication rates of percutaneous transthoracic needle biopsy

Objective To investigate the association of smoking with the outcomes of percutaneous transthoracic needle biopsy (PTNB). Methods In total, 4668 PTNBs for pulmonary lesions were retrospectively identified. The associations of smoking status (never, former, current smokers) and smoking intensity (≤ 20, 21–40, > 40 pack-years) with diagnostic results (malignancy, non-diagnostic pathologies, and false-negative results in non-diagnostic pathologies) and complications (pneumothorax and hemoptysis) were assessed using multivariable logistic regression analysis. Results Among the 4668 PTNBs (median age of the patients, 66 years [interquartile range, 58–74]; 2715 men), malignancies, non-diagnostic pathologies, and specific benign pathologies were identified in 3054 (65.4%), 1282 (27.5%), and 332 PTNBs (7.1%), respectively. False-negative results for malignancy occurred in 20.5% (236/1153) of non-diagnostic pathologies with decidable reference standards. Current smoking was associated with malignancy (adjusted odds ratio [OR], 1.31; 95% confidence interval [CI]: 1.02–1.69; p = 0.03) and false-negative results (OR, 2.64; 95% CI: 1.32–5.28; p = 0.006), while heavy smoking (> 40 pack-years) was associated with non-diagnostic pathologies (OR, 1.69; 95% CI: 1.19–2.40; p = 0.003) and false-negative results (OR, 2.12; 95% CI: 1.17–3.92; p = 0.02). Pneumothorax and hemoptysis occurred in 21.8% (1018/4668) and 10.6% (495/4668) of PTNBs, respectively. Heavy smoking was associated with pneumothorax (OR, 1.33; 95% CI: 1.01–1.74; p = 0.04), while heavy smoking (OR, 0.64; 95% CI: 0.40–0.99; p = 0.048) and current smoking (OR, 0.64; 95% CI: 0.42–0.96; p = 0.04) were inversely associated with hemoptysis. Conclusion Smoking history was associated with the outcomes of PTNBs. Current and heavy smoking increased false-negative results and changed the complication rates of PTNBs. Clinical relevance statement Smoking status and intensity were independently associated with the outcomes of PTNBs. Non-diagnostic pathologies should be interpreted cautiously in current or heavy smokers. A patient’s smoking history should be ascertained before PTNB to predict and manage complications. Key Points • Smoking status and intensity might independently contribute to the diagnostic results and complications of PTNBs. • Current and heavy smoking (> 40 pack-years) were independently associated with the outcomes of PTNBs. • Operators need to recognize the association between smoking history and the outcomes of PTNBs. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-024-10705-8.

All the percutaneous transthoracic needle biopsy (PTNB) procedures were performed either by board-certified thoracic radiologists under the supervision of attending thoracic radiologists or attending thoracic radiologists alone.The majority of the PTNB procedures were performed by thoracic radiologists taking part in fellowship training, who started their training in March or May of each year.There were usually 2 or 3 thoracic radiologists in fellowship training each year, and they usually rotated thoracic intervention schedules (including PTNB procedures) for 2 to 3 months.Attending thoracic radiologists performed the minority of PTNBs.Two conebeam CT machines were used during the study period (Axiom Artis dTA/VB30, Siemens; Allura Xper FD20, Philips Healthcare).
If there were multiple candidates for PTNBs, the target lesion was selected by the operators with consideration of the yield and potential complication risks; therefore, peripherally located lesions, larger lesions, or lesions not abutting vessels or emphysematous cysts were usually selected.The PTNB technique (coaxial technique vs. fine-needle aspiration only) and needle size were chosen by the operators [1][2][3][4].After introducing the needle, cone-beam CT scanning was performed to identify whether the tip of the needle was located properly, and if needed, the needle tip was adjusted under cone-beam fluoroscopic guidance to obtain optimal pathologic specimens.On-site pathologists did not attend the PTNB procedures, and the operators chose the number of tissue samples based on the adequacy of the PTNB specimens according to factors such as the specimens' length, thickness, and color.The needle indwelling time (fine-needle aspiration: time interval between initial needle insertion and final needle removal; core needle biopsy: time interval between the insertion and removal of core needle) was routinely recorded by the radiology technicians.

Method S2. Details of Collected Data
Information on target lesions, such as the lesion location, lesion size, and lesion type (solid vs. part-solid), was collected from standardized PTNB reports.Operators assessed the presence of emphysema based on preprocedural CT findings.Information on the PTNB procedures, including the pleura-to-target distance, the position during the PTNB procedure, biopsy needle size, the number of pleural passages, the number of tissue samples, and needle indwelling time, was also collected in the same manner.In addition, the presence of emphysema along the needle tract, the presence of the open bronchus sign in the target lesion, and the presence of spiculation at the target lesion were also identified based on preprocedural CT findings.
The operators recorded complications (pneumothorax, pneumothorax requiring chest drainage catheter insertion, or hemoptysis) in PTNB reports by reviewing post-PTNB followup images and electronic medical records.The development of immediate pneumothorax or non-immediate pneumothorax during the admission period was defined as the presence of pneumothorax.The first author (W.H.L) reviewed procedural and post-procedural images to identify pneumothorax.A study coordinator curated the pathologic results of PTNB specimens from patients' electronic medical records.

Method S3. Details of the Logistic Regression Analysis
This study considered the operators' proficiency in PTNB procedures and the difficulty of PTNB procedures because these factors might be associated with the outcomes of the PTNBs.
In detail, reflecting the annual schedule of fellowship training, the operators were thought to have less experience in PTNBs if the procedures were performed between March and August of each year, whereas the PTNBs being performed between September and February of each year were considered to be performed by thoracic radiologists with sufficient experience in PTNBs [5].The analyses adjusted for the proficiency of the operators, the presence of emphysema along the needle tract (one of the major risk factors for pneumothorax requiring catheter drainage), the presence of the open bronchus sign in the target lesion (one of the major risk factors for hemoptysis), and needle indwelling time (a surrogate for the difficulty of the PTNB procedure and the operators' experience) [1,5,6].
To focus on the effect of smoking on the diagnostic results and complications of PTNB procedures, logistic regression was performed with adjustment for the following covariates based on previous studies: 1) diagnosis of malignancies: age, sex, location of the lesion, size, lesion type (solid vs. part-solid), the presence of spiculation, the presence of emphysema, the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,[5][6][7]; 2) non-diagnostic pathologies: age (> 65 years vs. ≤ 65 years), sex, size (≤ 1 cm, > 1 cm and ≤ 2 cm, > 2 cm and ≤ 3 cm, or > 3 cm), lesion type (solid vs. part-solid), procedure with fine-needle aspiration only, the number of tissue samples with a cutting needle (≥ 3 vs.< 3), position during the PTNB procedure (supine, prone, or lateral decubitus), the presence of hemoptysis, the final diagnosis (malignancy vs. benign), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,8,9]; 3) false-negative results in non-diagnostic pathologies: age (> 65 years vs. ≤ 65 years), sex, the presence of emphysema, location of the lesion, lesion type (solid vs. part-solid), the category of non-diagnostic pathologies (non-specific benign, atypical cells, or insufficient for diagnosis), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,9]; 4) false-negative results in non-specific benign pathologies: age (> 65 years vs. ≤ 65 years), sex, the presence of emphysema, lesion type (solid vs. part-solid), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,9]; 5) pneumothorax: age (≥ 60 years vs. < 60 years), sex, location of the lesion, size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2 cm and ≤ 4 cm, or > 4 cm), the number of pleural passages (1, 2, or > 2), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,10], 6) pneumothorax requiring chest drainage catheter insertion: age (≥ 60 years vs. < 60 years), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2 cm and ≤ 4 cm, or > 4 cm), the number of pleural passages (1, 2, or > 2), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,10]; and 7) hemoptysis: sex, size (> 2 vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2 cm and ≤ 4 cm, or > 4 cm), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience) [1,5,6,10].
In multivariable logistic regression analysis with backward elimination (as sensitivity analyses), the full models included the following variables: 1) diagnosis of malignancies: smoking status (never, former, or current smokers), pack-year category (≤ 20, > 20 and ≤ 40, or > 40), age (> 65 years vs. ≤ 65 years), sex, location of the lesion (upper or middle lobe vs. lower lobe), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, the presence of spiculation, the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience); 2) non-diagnostic pathologies: smoking status (never, former, or current smokers), pack-year category (≤ 20, > 20 and ≤ 40, or > 40), age (> 65 years vs. ≤ 65 years), sex, location of the lesion (upper or middle lobe vs. lower lobe), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2cm and ≤ 4 cm, > 4 cm), position during the PTNB procedure (supine, prone, or lateral decubitus), needle size (18G vs. smaller than 18G), procedure with fine-needle aspiration only, the number of pleural passages (1 vs. multiple), the number of tissue samples with a cutting needle (< 3 vs.≥ 3 times), the presence of pneumothorax, the presence of hemoptysis, the final diagnosis (malignancy vs. benign), the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience); 3) false-negative results in non-diagnostic pathologies: smoking status (never, former, or current smokers), pack-year category (≤ 20, > 20 and ≤ 40, or > 40), age (> 65 years vs. ≤ 65 years), sex, location of the lesion (upper or middle lobe vs. lower lobe), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-totarget distance (≤ 2 cm, > 2 cm and ≤ 4 cm, or > 4 cm), position during the PTNB procedure (supine, prone, lateral decubitus), needle size (18G vs. smaller than 18G), procedure with fineneedle aspiration only, the number of pleural passages (1 vs. multiple), the number of tissue samples with a cutting needle (< 3 vs.≥ 3), the presence of pneumothorax, the presence of hemoptysis, the category of non-diagnostic pathologies (non-specific benign pathologies, atypical cells, or insufficient for diagnosis) the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience); 4) pneumothorax and pneumothorax requiring chest drainage catheter insertion: smoking status (never, former, or current smokers), pack-year category (≤ 20, > 20 and ≤ 40, or > 40), age (> 65 years vs. ≤ 65 years), sex, location of the lesion (upper or middle lobe vs. lower lobe), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2cm and ≤ 4 cm, or > 4 cm), position during the PTNB procedure (supine, prone, or lateral decubitus), needle size (18G vs. smaller than 18G), procedure with fine-needle aspiration only, the number of pleural passages (1 vs. multiple), the number of tissue samples with a cutting needle (< 3 vs.≥ 3), the presence of hemoptysis, the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the less-experienced period vs. after sufficient experience); 5) hemoptysis: smoking status (never, former, current smokers), pack-year category (≤ 20, > 20 and ≤ 40, or > 40), age (> 65 years vs. ≤ 65 years), sex, location of the lesion (upper or middle lobe vs. lower lobe), size (> 2 cm vs. ≤ 2 cm), lesion type (solid vs. part-solid), the presence of emphysema, pleura-to-target distance (≤ 2 cm, > 2cm and ≤ 4 cm, or > 4 cm), position during the PTNB procedure (supine, prone, or lateral decubitus), needle size (18G vs. smaller than 18G), procedure with fine-needle aspiration only, the number of pleural passages (1 vs. multiple), the number of tissue samples with a cutting needle (< 3 vs.≥ 3), the presence of pneumothorax, the presence of emphysema along the needle tract, the presence of the open bronchus sign, needle indwelling time, and the operators' experience (during the lessexperienced period vs. after sufficient experience).
The associations of lung cancer screening eligibility with the diagnostic results and complication rates of PTNB procedures were also explored: 1) U.S. Preventive Services Task Force (USPSTF) lung cancer screening eligibility (ever-smoker, age of 50 to 80 years with at least a 20 pack-year smoking history, current smoker or former smoker having quit smoking within the past 15 years) [11]; National Comprehensive Cancer Network (NCCN) lung cancer screening eligibility (ever-smoker, age equal to or more than 50 years with at least a 20 packyear smoking history) [12]; and National Lung Screening Trial (NLST) eligibility (ever-smoker, age of 55 to 74 years with at least a 30 pack-year smoking history, current smoker or former smoker having quit smoking within the past 15 years) [13].Patients whose cessation duration could not be documented through their electronic medical records were not considered eligible for screening according to the USPSTF and NLST criteria.Since eligibility for lung cancer screening was determined in terms of age and pack-years, logistic regression was performed without adjusting for those covariates to explore the effect of lung cancer screening eligibility on PTNB procedures.  1 (0.8%) 4 (7.4%) 6 (11.1%) a "Neuroendocrine neoplasm, other than small cell carcinoma" included typical or atypical carcinoid, or large cell neuroendocrine carcinoma.b The "others" category included adenosquamous carcinoma or sarcomatoid carcinoma.a From 4539 PTNB procedures with decidable reference standards.

Supplementary Tables
b The Firth correction was applied.
c From 1153 non-diagnostic pathologies with decidable reference standards.
d From 969 non-specific benign pathologies with decidable reference standards.

Table S6 .
Results of Multivariable Logistic Regression with Backward Elimination in AllPatients

Table S7 .
Results of Multivariable Logistic Regression with Backward Elimination Regarding the Effect of Lung Cancer Screening Eligibility on Percutaneous Transthoracic Needle Biopsy Details of Percutaneous Transthoracic Needle Biopsy Procedures

Table S1 .
Characteristics of Lung Cancer Screening-Eligible Individuals a Median [interquartile range].bFrom 1651 patients with documented cessation duration.

Table S2 .
Outcomes of Percutaneous Transthoracic Needle Biopsy Procedures According tothe Operators' Experience From 969 non-specific benign pathologies with decidable reference standards.

Table S3 .
Detailed Results of Percutaneous Transthoracic Needle Biopsy with False-Negative Results

Table S4 .
Detailed Results of Logistic Regression Analysis After Adjusting for Covariates