Overview

Nowadays, it is challenging even for experienced doctors to determine the causes of lymphocytosis (high lymphocyte count) in their patients. If you’re affected by lymphocytosis, you are not alone, and growing evidence could help clarify the underlying problem. Smoking is a common but underrecognised cause of lymphocytosis. Studies show that over 50% of smokers suffering from leukocytosis (high white blood cell count) also have high lymphocyte counts, which usually normalise after quitting. Understanding the link between smoking and lymphocytosis can help avoid unnecessary tests and misdiagnosis. Let’s explore how this mild condition is sometimes mistaken for more severe haematological illnesses. 

Introduction 

Leukocytosis is an increase in the total number of white blood cells (WBCs). It is an umbrella term, as leukocytosis can be defined and categorised by the type of WBC that is elevated.⁶ 

Leukocytosis has various causes such as infections, allergies, smoking and, in some cases, cancer. Leukocytosis is usually considered a mild condition, but it can indicate more severe diseases such as leukaemia and lymphoma.⁶ 

Lymphocytosis is an increase in the number of lymphocytes, a type of white blood cell.⁵ The most common cause of lymphocytosis is viral infections, as lymphocytes are commonly involved in fighting infections.⁵ However, research has indicated that lymphocyte levels were increased in smokers when compared to non-smokers, as well as an increase in overall WBCs.^2,7

This article will explore the effects smoking tobacco and cigarettes has on the body and blood test results, with a focus on leukocytosis and, more specifically, lymphocytosis.

What is smoking-related lymphocytosis?

A lot of research has demonstrated that smoking tobacco and cigarettes has been linked to many health conditions, including hypertension, hyperlipidemia and changes in the number of various blood cells (red and white blood cells) and components (haemoglobin).^8,9 More specifically, some studies have shown a direct link between smoking and leukocytosis when compared to non-smokers.^4,7 More recent studies have found that many smokers presented with lymphocytosis, which stabilised once they quit smoking, showing that smoking has a direct but reversible effect on lymphocyte numbers.^3,7 The reasons as to why smoking can affect WBC count are not entirely understood. However, researchers suspect it’s due to several inflammatory processes triggered by frequent exposure to the chemicals in cigarettes.⁹ It is essential for clinicians to understand the link between smoking and lymphocytosis, as this can reduce misdiagnosis of more serious conditions.

Epidemiology and clinical features

Typically, leukocytosis depends on several factors, such as age, sex, body mass index, and overall health.⁷ Although not the most common cause of lymphocytosis, smoking has been reported to have a frequent impact on WBC levels. A recent study found that 53% of smokers who participated presented with asymptomatic lymphocytosis, indicating the cause to be an autoimmune response.³ Another study found that not only smokers present with higher lymphocyte levels when compared to non-smokers, but that smoking had a link with a specific type of lymphocytosis called persistent polyclonal B cell lymphocytosis (PPBL).⁴ Additionally, it was found during this study that PPBL was seen more frequently in women who were heavy smokers and was often permanent in these specific circumstances.⁴

Clinically, most cases of leukocytosis or lymphocytosis (including PPBL) are asymptomatic, reversible, and harmless, except in cases of certain infections, conditions or cancer.⁵ However, it still remains essential for clinicians to be aware of the links between smoking and the increase in WBCs due to its usual harmless effects, to prevent unnecessary medical tests.

Why is it underrecognised?

Smoking-related lymphocytosis remains underrecognised due to the fact that it presents as a mild, asymptomatic condition. Clinicians become concerned only when lymphocytosis presents with meaningful symptoms, such as those seen in blood cancers like leukaemia and lymphoma.^5,6 Although several studies have managed to find a direct link between smoking and lymphocytosis, these studies also reported that no obvious illness or symptoms were linked to the increase in lymphocytes.^2,4 Additionally, when an individual quits smoking, their lymphocyte and other WBC levels have returned to normal, which has been observed across many studies.^2-4 However, these levels may take some time to return to the normal levels seen in non-smokers, and it is rarely discussed with individuals looking to quit. This information should be considered by clinicians when offering smoking cessation advice and carrying out diagnostic tests on individuals who have recently quit smoking.^10,11

Implications for clinical practice

Many blood test results that indicate lymphocytosis can usually be explained by infection or certain health conditions. Clinicians should consider the smoking status of their patients when carrying out blood tests, as studies have shown that many individuals who smoke do not present with any conditions that would raise concerns.¹ By considering a patient’s smoking status, clinicians can avoid performing unnecessary tests, reducing both patient anxiety, harm and medical costs. In the cases where lymphocytosis is unexplained and asymptomatic, clinicians should consider smoking as a cause, as plenty of research supports that there is a direct link.

Furthermore, acknowledging the link between smoking and lymphocytosis can become a helpful tool in motivating patients to quit smoking. A lot of changes caused by smoking can be reversed within weeks of quitting, including some levels of WBCs.¹ Other studies have shown that lymphocytosis reversal is more gradual, requiring months or years, depending on the extent of smoking.^7,11 Understanding the link between smoking and lymphocytosis can improve all round patient experience and care by decreasing the risk of unnecessary testing.

Diagnostic approach

If a smoker has lymphocytosis, doctors should initiate a focused diagnostic approach before proceeding with complicated tests. A detailed smoking history should be considered the first step when exploring the cause of lymphocytosis, including calculating pack years to determine the extent of a patient’s smoking, alongside a complete blood count (CBC). Clinicians can suspect smoking-related lymphocytosis if the elevation is mild or moderate and the patient does not have any symptoms like fever, weight loss, or swollen lymph nodes.^5,6 

Extra observations may be necessary in certain circumstances. Studies have shown that in rare circumstances, some heavy smokers who were women developed PPBL even after quitting.⁴ In these cases, long-term observation may be beneficial to these patients, as reversal of PPBL can take a long time to return to normal. Additionally, although most cases remain stable, it is still important to rule out lymphomas.¹² Observations may include bone marrow testing, flow cytometry and peripheral blood smears to rule out cancer.⁵

Summary

To summarise, smoking is a direct cause of mild and reversible lymphocytosis, which is frequently missed in clinical practice. The majority of smokers also showed elevated lymphocyte levels without any symptoms, which normalise after they stop smoking. This makes it highly important to include smoking in the differential diagnosis of lymphocytosis, to reduce unnecessary tests and patient anxiety. When evaluating lymphocytosis, doctors must take a detailed smoking history and interpret the blood results accordingly. Keeping clinicians up-to-date on smoking-related lymphocytosis would reduce the cost of medicines and raise the diagnostic accuracy. If smoking were recorded in clinical guidelines as a cause of lymphocytosis, it could facilitate the standardisation of diagnosis and treatment. Recognising the relationship promotes targeted research and offers an opportunity to support smoking cessation for better patient care over time.