The study was performed at a mill where soft tissue paper production started on a small scale in 1948, and increased considerably around 1960. Today, the mill is one of the largest soft paper plants in Sweden. In 2006, all employees currently working at the mill (n = 205) were invited to participate in a clinical investigation at the mill site. Six of the invited persons did not participate. Hence, the initial study population included 199 workers.
All invited workers received an extensive questionnaire with questions about occupational history, smoking habits, and respiratory symptoms and asthma. Height and weight were measured with workers wearing light clothing and no shoes. Spirometry without bronchodilation was performed with a dry wedge spirometer (Vitalograph, Buckingham, UK) and according to American Thoracic Society (ATS)/European Respiratory Society (ERS) standards (Miller et al. 2005). Forced vital capacity and FEV1 were measured with individuals in a sitting position and wearing a nose clip, and predicted normal values were based on the GLI-equations (Quanjer et al. 2012). Blood samples were analyzed for specific immunoglobulin E class using Phadiatop analysis (Pharmacia & Upjohn Diagnostics, Uppsala, Sweden).
Different definitions of airflow limitation (AL) were used: ALGOLD was defined, according to Global Initiative for Obstructive Lung Disease (GOLD) criteria, as an FEV1/FVC ratio of < 0.7 (Vogelmeier et al. 2017); ALLLN was defined as an FEV1/FVC ratio below the lower limit of normal (LLN5) (Quanjer et al. 2012). Restrictive spirometric pattern was defined as FEV1/FVC > 0.7 and FVC < 80% predicted (Crapo 1994).
Smoking was classified as never-smoking, former smoking, and current smoking, based on the subjects’ answers to the questionnaire. Pack-years were calculated among current and former smokers. Asthma was defined as an affirmative answer to “Have you ever had asthma diagnosed by a physician?” and onset after 15 years of age (Torén et al. 1993). Cough with phlegm (chronic bronchitis) was defined as an affirmative answer to “Have you had long-standing cough with phlegm?” and “If so, did any period last at least 3 months?” and “If so, have you had such periods at least 2 years in a row?” (Holm et al. 2014). Wheezing was defined as an affirmative answer to the question “Have you experienced wheeze or whistling in your chest at any time since 15 years of age?” Atopy was defined as a positive Phadiatop result (class 1) (Matricardi et al. 1990). Body mass index (BMI) was defined as measured weight/height2.
For the purpose of this study, we developed a specific job exposure matrix (JEM) for soft paper dust exposure. Exposure to soft paper dust was assessed from historical stationary and personal measurements of total dust, in addition to historical information about the work, department where worked, and kind of production, allowing us to assess exposure to soft paper dust for every year for each worker with an estimated mean level of dust (mg/m3). Further, the cumulative exposure, in mg/m3-years, was calculated for each worker, as (mg/m3) × years of exposure. Due to variations in exposure across time and duties, most workers were classified into more than one exposure category over the study period. The cumulative number of years in different exposure categories is shown in Table 1. Cumulative mg/m3-years for all workers were divided into quartiles and workers in the highest quartile (> 72 mg/m3-years) were defined as high exposed. The remaining workers were classified as lower exposed. High exposed years were defined as years having been exposed to soft paper dust exceeding 5 mg/m3.
In the univariate analyses, we dichotomized the subjects into high exposed and lower exposed to soft paper dust. Univariate inferential analyses were performed using Chi-square test and Student’s t test. Where there were fewer than ten subjects in any stratum, Fisher’s exact test was used for univariate analyses. Univariate analysis results were considered significant if p < 0.05.
Lung function outcomes (dependent variable) and the association between the different independent variables (gender, BMI, pack-years, current smoking, atopy, and soft paper dust exposure) were examined in multiple linear regression models, and also stratified into never-smoking and ever-smoking. The associations between high exposure (highest quartile of cumulative dust exposure) and ALGOLD, ALLLN, asthma, chronic bronchitis, and wheezing were analyzed using logistic regression models. Dust exposure was measured in terms of high exposed years as well as the cumulative exposure measure, mg/m3-years. All variables were kept in the models even if most of them were without formal statistical significance. The models were adjusted for former and current smoking and also stratified into never-smoking and ever-smoking. In all regression models, we used 95% confidence intervals (CIs) and p values to determine significance. All analyses were performed using SAS version 9.4 (SAS, Cary, NC, USA).