Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey

Abstract

BackgroundThis study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP.MethodsWe retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups.ResultsOf the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P < 0.001) and had significantly lower PaO2 and DLCO with higher D(A-a)O2 at the onset of disease than those without lavage (n = 40) (P = 0.006, P < 0.001, and P = 0.036, respectively). Correspondingly, the distribution of disease severity score (DSS) differed significantly between the two groups (P = 0.001). Based on these, when the total patients were categorized according to DSS (low DSS [DSS 1–2] vs. high DSS [DSS 3–5]), smoking status differed significantly between the two groups with the proportion of current smokers significantly higher in the high DSS group (11/22 [50%] vs. 7/39 [17.9%], P = 0.008). Furthermore, current smokers had meaningfully higher DSS and serum CEA levels than non-current smokers (P = 0.011 and P = 0.031), whereas no difference was found between smokers and non-smokers. Regarding type of exposed dust, farming dust was significantly associated with more severe form of PAP (P = 0.004).ConclusionA considerable proportion of PAP patients had a history of cigarette smoking and/or dust exposure, suggestive of their possible roles in the development of PAP. Active cigarette smoking at the onset of PAP is associated with the severity of PAP.

A Case of Autoimmune Pulmonary Alveolar Proteinosis with Pulmonary Fibrosis and Asbestosis-Like Features

“…[12] Moreover, previous studies suggested that an exposure to material can lead to the production of anti-GM-GSF autoantibody [13][14]. The percentage of autoimmune PAP patients who also had inhalational exposure varies between 26% and 54% in studies [3,[15][16][17][18]. Although the present case had asbestosis-like findings including asbestos bodies and pleural thickening on HRCT, no typical ra-diological findings such as a subpleural dotlike opacity, subpleural curvilinear line, or parenchymal band were observed.…”

Pulmonary alveolar proteinosis with upper‐lobe predominance in a non‐smoking female

“…It is about two‐fold more common in male than in female, and is more common in smokers or those with a positive history of causative exposure. The onset is usually insidious, with such non‐specific symptoms as dyspnoea, cough, fatigue, and occasionally fever . Pulmonary function tests almost consistently reveal a reduction in the DLco indicating the presence of ventilation‐perfusion mismatch, with or without a restrictive‐type ventilatory deficit .…”

“…Hereditary PAP is caused by mutations in genes encoding subunits of GM‐CSF receptors . For non‐hereditary PAP, most cases are due to the presence of anti‐GM‐CSF auto‐antibodies that disrupt the signalling of the cytokine (“auto‐immune PAP”) , while the rest have “secondary PAP” that is either triggered by extrinsic stimuli (such as particles and fumes) or caused by an underlying condition (such as infection or hematologic disorders) that impairs the number or function of alveolar macrophages .…”

Pulmonary alveolar proteinosis in Korea: analysis of prevalence and incidence via a nationwide population-based study

“…In Asian countries including Korea, PAP was reported to be more prevalent in men, but the male-to-female ratio was relatively lower when compared with that of Western countries (1.3-2.1 [Asian] vs. 2.4-4.0 [Western]) [4,5,8,10,12,13]. In addition, the age at diagnosis of Asian patients was usually higher (mean age: 47.5-52 vs. 34-49 years) [4,5,8,10,12,13]. These results may reflect the genetic and environmental differences of Asian patients with PAP; however, these previous studies in Asia may have biased results since they included only selected patients who visited 10-15 referral medical institutes or those enrolled in the national PAP registry [4,12,13].…”

“…In addition, the age at diagnosis of Asian patients was usually higher (mean age: 47.5-52 vs. 34-49 years) [4,5,8,10,12,13]. These results may reflect the genetic and environmental differences of Asian patients with PAP; however, these previous studies in Asia may have biased results since they included only selected patients who visited 10-15 referral medical institutes or those enrolled in the national PAP registry [4,12,13]. Therefore, in order to overcome these limitations, epidemiological studies based on entire populations are needed for rare diseases such as PAP.…”