What causes elevated neutrophil counts in a patient, potentially with a history of chronic conditions such as Chronic Obstructive Pulmonary Disease (COPD) or Diabetes Mellitus (DM)?

Elevated Neutrophil Counts: Causes and Clinical Significance

Bacterial infection is the most common and clinically important cause of elevated neutrophils, particularly when accompanied by a left shift (increased band forms), and should be the primary consideration in any patient with neutrophilia. 1, 2

Primary Causes of Neutrophilia

Infectious Causes (Most Common)

Bacterial infections are the leading cause of neutrophilic leukocytosis and require immediate evaluation:

• An elevated absolute band count ≥1,500 cells/mm³ has the highest diagnostic value (likelihood ratio 14.5) for documented bacterial infection 1, 2
• A neutrophil percentage >90% carries a likelihood ratio of 7.5 for bacterial infection 1, 2
• A left shift (≥16% band neutrophils) has a likelihood ratio of 4.7 for bacterial infection, even when total WBC count is normal 1, 2
• Common bacterial infections causing neutrophilia include respiratory tract infections, urinary tract infections, skin/soft tissue infections, and gastrointestinal infections 2
• Septicemia is associated with high-grade leukocytosis (WBC >20,000 cells/mm³) and increased mortality risk 1

Chronic Inflammatory Conditions

In patients with chronic diseases like COPD or diabetes:

• Chronic inflammation is characterized by persistent neutrophil activation and contributes to disease progression in conditions such as atherosclerosis, diabetes mellitus, and COPD 3
• Neutrophils in COPD demonstrate both eosinophilic and neutrophilic airway inflammation patterns, with neutrophilic bronchitis present in approximately 19% of patients with asthma-COPD overlap 4
• Systemic inflammation in chronic diseases shows elevated IL-6, C-reactive protein, and tumor necrosis factor-α 4
• Neutrophil counts within the "normal" range (6-7 × 10⁹/L versus 2-3 × 10⁹/L) are strongly associated with cardiovascular complications including heart failure (HR 2.04) and peripheral arterial disease (HR 1.95) 5

Physiological and Medication-Related Causes

Non-infectious causes must be systematically excluded:

• Corticosteroids, lithium, and beta-agonists are the most common medications causing neutrophilia 2, 6
• Emotional stress and acute exercise trigger neutrophilia through catecholamine and cortisol release 6
• Lithium therapy consistently causes leukocytosis; WBC <4,000/mm³ would be unusual in lithium-treated patients 6

Malignancy-Related Neutrophilia

• Solid tumors, particularly when necrotic or causing obstruction, can produce neutrophilic leukocytosis 1
• Adult-onset Still's disease causes striking neutrophilia, with 50% of patients having WBC >15×10⁹/L and 37% having WBC >20×10⁹/L 1, 6
• Extreme leukocytosis (>100,000/mm³) represents a medical emergency due to risk of cerebral infarction and hemorrhage 6

Diagnostic Approach in Patients with Chronic Conditions

Initial Assessment

Order a complete blood count with manual differential (not automated) to assess:

• Absolute neutrophil count and band forms 2, 6
• The presence of left shift indicating bacterial infection 2
• Manual differential is preferred over automated counts to accurately assess bands and immature forms 2

Clinical Evaluation Priority

1. Systematically evaluate for infection sources: fever, localizing symptoms (respiratory, urinary, abdominal pain, skin lesions), or signs of sepsis 2, 6
2. Review current medications: corticosteroids, lithium, beta-agonists 6
3. Consider recent physical or emotional stress 6
4. In patients with cirrhosis and ascites, perform diagnostic paracentesis if neutrophil count suggests spontaneous bacterial peritonitis (>250 cells/mm³ in ascitic fluid) 2

Additional Testing When Indicated

• Blood cultures if systemic infection is suspected 2
• Urinalysis with culture for urinary symptoms 2
• Chest imaging for respiratory symptoms 2
• Site-specific cultures as indicated 2

Critical Clinical Pitfalls to Avoid

Do not overlook these common errors:

• Never ignore elevated neutrophil percentage (e.g., 84%) when total WBC is normal—left shift can occur with normal WBC and still indicate serious bacterial infection 2, 6
• Do not assume absence of infection based on normal or low WBC—bacterial infections can present with leukopenia, particularly in elderly or immunosuppressed patients 6
• Do not treat asymptomatic patients with antibiotics based solely on mildly elevated neutrophil counts without clinical evidence of infection 1, 6
• Serial measurements are more informative than single values for unexplained persistent elevation 6
• In COPD patients, recognize that neutrophilic inflammation may represent disease-related chronic inflammation rather than acute infection 4

Special Considerations for COPD and Diabetes Patients

• Chronic low-grade systemic inflammation in these conditions contributes to elevated baseline neutrophil counts 3
• Neutrophil activation markers (such as calprotectin) may be chronically elevated 7
• Even "normal range" neutrophil counts (3-4 versus 2-3 × 10⁹/L) confer increased cardiovascular risk in these populations 5
• Acute elevations above baseline warrant evaluation for superimposed bacterial infection 1, 2