Smoking at any time in life leads to poorer outcomes in AAV: Study

Mortality rate found to be significantly higher in patients who smoke

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Smoking at any time during one’s lifetime leads to more advanced disease and worse prognosis for people with ANCA-associated vasculitis (AAV), according to a 32-year study in Poland.

Specifically, current or past smoking is linked to higher disease activity at diagnosis, and a greater need for kidney replacement and immunosuppressive treatments, findings show.

The single-center retrospective study also identified smoking and being male as independent risk factors for mortality in AAV patients.

“This provides an improved insight into the impact of smoking as an environment trigger for AAV and highlights the need for further research into this link,” researchers wrote.

The study, “Influence of smoking on disease activity and prognosis of ANCA-associated vasculitis: a retrospective cohort study,” was published in the journal Polish Archives of Internal Medicine.

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Research suggests genetic and environmental factors contribute to AAV onset

AAV is a group of autoimmune diseases characterized by the production of self-reactive antibodies, called ANCAs, that cause inflammation and damage to the body’s small blood vessels in key organs, such as the lungs and kidneys.

While the specific cause of AAV is unclear, research suggests that both genetic and environmental factors can contribute to its onset.

Smoking has been associated with the development of certain autoimmune diseases. However, its role in AAV remains controversial, with some studies reporting a link between smoking and a higher risk of AAV, and others suggesting an inverse link. Moreover, whether smoking impacts the prognosis and survival of patients remains unknown.

To fill this knowledge gap, researchers in Poland retrospectively analyzed data from 223 AAV patients (46% women) who were followed for 32 years (October 1988 to August 2020) at the Medical University of Gdansk, in Poland.

Mean age at diagnosis was 53.3 years. A total of 116 were classified as never-smokers at the time of their diagnosis, and the remaining 107 patients as ever-smokers — 68 past smokers and 39 current smokers. A significantly greater proportion of ever-smokers were men relative to non-smokers (71% vs. 39%).

Results showed that the time between symptom onset and AAV diagnosis was significantly shorter for patients who smoked, either currently or in the past, than for those who never did (mean of four vs. six months).

This provides an improved insight into the impact of smoking as an environment trigger for AAV and highlights the need for further research into this link.

Kidney replacement therapy needed more frequently in smokers group

Organ involvement and symptoms in the ever-smokers group were similar to those who had never smoked, but kidney replacement therapy was significantly more frequent among ever-smokers (31% vs. 14%).

Kidney replacement therapy, as the name suggests, includes procedures such as dialysis that replace the kidneys’ role in removing waste products and excess fluid from the blood.

Also, ever-smokers showed significantly greater disease activity than never-smokers, as shown by higher scores in the Birmingham Vasculitis Activity Index version three (mean of 19 vs. 17.25). No significant group differences were seen in terms of disease extent index, disease stage onset, number of relapses, and time to relapse.

Blood work was also similar between the groups, including in ANCA-related statuses. The exception was the median levels of C-reactive protein, a marker of general inflammation, which were significantly elevated in the ever-smokers.

While no group differences were seen in terms of immunosuppressive treatment, ever-smokers received cyclophosphamide significantly more often than never-smokers (92% vs. 81%).

The mortality rate was significantly higher for ever-smokers than never-smokers (23% vs. 9%), and further statistical analysis showed that ever-smokers had a nearly threefold higher risk of dying than never-smokers.

Having smoked, currently or in the past, and being male were identified as independent predictors of mortality in AAV patients. Specifically, smoking was linked to a twofold higher risk of death, while being male was associated with a 33% lower risk.

Male patients who had smoked or were smokers at diagnosis also had significantly greater mortality than those who never smoked (22% vs. 4%). Male ever-smokers were also significantly more likely to need kidney replacement therapy (36% vs. 18%) but less likely to show sinus involvement (30% vs. 53%) than never-smokers.

No significant differences in organ involvement or mortality were observed in female patients, regardless of smoking status.

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‘Smoking at any point in life predicts advanced disease and worse prognosis’

To further assess the impact of smoking on AAV, the researchers compared current smokers with past smokers.

They found that current smokers were significantly younger at diagnosis (mean 50.56 vs. 57.76 years) and more likely male (85% vs. 62%).

No other significant group differences were detected, with both groups showing comparable organ involvement, disease activity and severity, relapse-related measures, blood parameters, cyclophosphamide treatment, number of deaths, and mortality risk.

The absence of differences between past and current smokers suggest that “smoking at any point in life predicts advanced disease and worse prognosis of AAV,” the researchers wrote.

“Future multicenter studies are required to further characterize the clinical, biological,
and prognostic impact of smoking on AAV,” the team concluded.