Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Using Sputum Cytology to Predict COPD Exacerbations

  Chronic obstructive pulmonary disease (COPD) exacerbations are periods of worsening breathlessness, cough, sputum volume, or sputum purulence that require additional treatment. They accelerate lung-function decline, reduce quality of life, and frequently lead to emergency visits or hospitalization. Predicting which patients are approaching a flare remains a major goal in respiratory medicine.

  Sputum cytology offers a practical way to examine airway inflammation directly. By assessing inflammatory cells and epithelial elements in expectorated or induced sputum, clinicians may identify patterns associated with eosinophilic or neutrophilic airway disease. The method is inexpensive compared with many molecular tests, although its predictive value depends on sample quality, timing, and interpretation.

  Why Airway Cell Profiles Matter

  COPD is biologically heterogeneous. Some patients have predominantly neutrophilic inflammation, while others show increased eosinophils, bacterial colonization, mucus hypersecretion, or overlapping features of asthma. These patterns can change over time and may differ between stable disease and an acute exacerbation.

  A sputum sample captures part of this local airway environment. A high neutrophil proportion may indicate persistent innate immune activation, while elevated eosinophils can point toward type 2 inflammation and a greater likelihood of responding to corticosteroids. Neither finding should be treated as an isolated forecast, but each can add context to symptoms, spirometry, prior exacerbations, and treatment history.

  What Sputum Cytology Measures

  Routine cytological assessment may report the proportions of neutrophils, eosinophils, macrophages, lymphocytes, bronchial epithelial cells, and squamous epithelial cells. It can also describe mucus, cellular degeneration, bacterial material, and occasional atypical cells. A differential cell count is often more clinically useful for COPD management than a simple descriptive examination.

  The collection method affects reliability. Spontaneously produced sputum is convenient, but saliva contamination can make the specimen difficult to interpret. Induced sputum, collected after inhalation of controlled concentrations of hypertonic saline, can provide a more representative lower-airway sample when performed by trained staff. Samples should be processed promptly, with clear reporting of adequacy and contamination.

  Cytology may identify abnormal cells that warrant separate evaluation, but it is not a substitute for imaging or a dedicated lung-cancer diagnostic pathway. The primary role in COPD is to characterize airway inflammation and support risk assessment.

  How Cell Patterns Relate to Exacerbations

  Neutrophilic inflammation is common in moderate-to-severe COPD and may be associated with frequent exacerbations, chronic bronchitis, and more intense mucus production. However, neutrophilia alone is not specific enough to predict an imminent event. It can also result from smoking, stable bacterial colonization, recent infection, or inhaled irritants.

  Sputum eosinophilia has a different clinical implication. Persistently elevated eosinophil counts may identify patients with an exacerbation-prone phenotype who are more likely to benefit from inhaled corticosteroid therapy, particularly when blood eosinophils and clinical history support the same interpretation. A single low or high result should be interpreted cautiously because eosinophil levels fluctuate with infection, corticosteroid exposure, and seasonal factors.

  The strongest prediction comes from combining cytology with established indicators: a history of two or more moderate exacerbations, a previous hospitalization, worsening dyspnea, increased sputum purulence, declining peak flow, poor medication adherence, and recent viral or bacterial infection. Cytology is best viewed as one component of a multidimensional risk model.

  Comparing Useful Sputum Findings

  The table below summarizes how common cytological patterns may contribute to clinical reasoning. These associations are not diagnostic thresholds, and laboratories may use different preparation and counting methods.

  Sputum finding	Possible clinical meaning	Relationship to exacerbation risk	Important limitation
  Increased neutrophils	Ongoing innate airway inflammation or infection	May accompany frequent or severe flares	Common in stable COPD and influenced by smoking
  Increased eosinophils	Type 2 airway inflammation	May indicate corticosteroid-responsive exacerbation risk	Values vary with treatment and sampling time
  Abundant mucus	Mucus hypersecretion and impaired clearance	Often linked with chronic bronchitis and recurrent symptoms	Does not identify the cause of a flare
  Numerous squamous cells	Saliva contamination	Weakens confidence in all reported results	Indicates that repeat collection may be needed
  Degenerated cells and organisms	Possible infection or poor specimen preservation	May support, but cannot establish, infectious exacerbation	Requires clinical and microbiological correlation
  Predominant macrophages	Chronic smoke or particulate exposure	Reflects airway burden more than near-term risk	Limited value as a stand-alone predictor

  Building Cytology Into Clinical Assessment

  A useful workflow begins with a baseline sample during stable disease, followed by repeat sampling when symptoms change. Comparing the patient with their own previous results may be more informative than applying a universal cutoff. A rising eosinophil fraction, increasing neutrophil burden, or a sudden change in mucus characteristics may provide an early warning when paired with clinical deterioration.

  Sample quality must be documented. The report should state whether sputum was spontaneous or induced, whether squamous-cell contamination was substantial, how many inflammatory cells were counted, and whether recent antibiotics or corticosteroids could have altered the findings. Without this information, apparent changes may reflect collection variability rather than true biological progression.

  Clinicians should also integrate spirometry, oxygenation, symptom scores, inhaler technique, vaccination status, comorbidities, and exposure history. Cytology cannot reliably distinguish every viral, bacterial, and noninfectious trigger, so microbiological testing and chest imaging may be necessary when fever, focal signs, hemoptysis, or unexplained hypoxemia is present.

  Making the Results Clinically Actionable

  Sputum cytology is most valuable when it changes a management decision. A repeated eosinophilic pattern may support an inhaled corticosteroid discussion in a patient with recurrent exacerbations, while persistent neutrophilic inflammation may emphasize smoking cessation, airway-clearance strategies, infection evaluation, and pulmonary rehabilitation. Treatment should follow established COPD guidance rather than cytology alone.

  Recommendations for responsible use include:

  • Obtain samples during stable disease and, when feasible, during a clinically important exacerbation for comparison.
  • Reject or repeat heavily saliva-contaminated specimens instead of overinterpreting unreliable cell counts.
  • Interpret sputum eosinophils alongside blood eosinophils, exacerbation history, asthma features, and corticosteroid exposure.
  • Use neutrophil predominance as an inflammatory clue, not as proof of bacterial infection.
  • Combine cytology with symptoms, lung function, prior events, microbiology, and imaging when assessing near-term risk.

  Research is still needed to establish standardized processing protocols, reproducible thresholds, and validated prediction models. Future approaches may combine cytology with inflammatory proteins, microbiome analysis, digital image recognition, and home-based monitoring. These tools could make airway-cell profiling more useful for personalized COPD care while reducing unnecessary treatment escalation.

  Respiratory teams can begin by incorporating high-quality sputum assessment into selected patients with recurrent exacerbations, chronic sputum production, or uncertain inflammatory phenotype. Used with clinical judgment and longitudinal follow-up, cytology can help transform a routine specimen into a clearer picture of airway activity and potential flare risk.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)