Decreased FEF50 as an Indicator of Comorbid Asthma and Persistent Airflow Limitation in Patients with Chronic Rhinosinusitis with Nasal Polyps: A Cross-Sectional Study
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent condition often associated with comorbid asthma, particularly refractory asthma. Despite the high prevalence of asthma in CRSwNP patients, a significant proportion of these cases remain undiagnosed. Additionally, persistent airflow limitation (PAL) is frequently observed in CRSwNP patients with comorbid asthma. Small airway dysfunction (SAD) has been identified in CRSwNP patients, even in the absence of asthma, and its severity correlates with the duration of asthma history. This study aimed to evaluate clinical characteristics, particularly small airway parameters, as indicators of comorbid asthma in CRSwNP patients and of PAL in those with comorbid asthma. Furthermore, the study compared the prevalence of SAD and PAL between asthma patients with and without CRSwNP.
Study Design and Methodology
This cross-sectional study was conducted at Beijing Tongren Hospital from September 2017 to September 2021. The study enrolled consecutive CRSwNP patients aged 18 years or older, diagnosed based on symptoms and endoscopic signs. Exclusion criteria included a smoking index greater than 10 pack-years, exposure to biomass fuel or chemical agents for the past six months or longer, systemic steroid treatment in the last four weeks, biologic therapy or immunosuppressive treatment, acute respiratory infection within the last two weeks, autoimmune or immunodeficiency diseases, and severe heart, kidney, or liver dysfunction. Patients with chronic obstructive pulmonary disease (COPD) were also excluded based on medical history, clinical signs, and computed tomography (CT).
CRSwNP patients were categorized into those with or without asthma based on the Global Initiative for Asthma (GINA) criteria. Variable airflow limitation was determined using spirometry, either on enrollment or from medical records. For patients with comorbid asthma showing pre-bronchodilator (BD) forced expiratory volume in one second (FEV1) less than 80% predicted or an FEV1/forced vital capacity (FVC) ratio less than 0.8, post-BD FEV1% predicted (FEV1%pred) and FEV1/FVC were measured 15 minutes after inhalation of 400 µg salbutamol. Patients with comorbid asthma were further grouped into those with or without PAL based on whether the post-BD FEV1/FVC ratio was less than 0.7.
Data Collection and Analysis
Demographic data, medical histories, and medication use were recorded. Clinical parameters assessed included eosinophil (EOS) counts in nasal secretions and peripheral blood, total and allergen-specific serum immunoglobulin (Ig) E levels, fractional exhaled nitric oxide (FeNO), inflammatory cells in nasal polyp tissues, pulmonary and small airway function tests (forced expiratory flow at 50% [FEF50], 75% [FEF75], and between 25% and 75% of FVC [MMEF]), and asthma severity. SAD was defined when at least two of the three small airway parameters were less than 65% of predicted values. Data from stable asthmatics without CRSwNP were also collected from September 2019 to September 2021 to compare the prevalence of SAD and PAL between asthma patients with and without CRSwNP.
Statistical analyses were performed using SPSS version 23.0. Data were expressed as mean ± standard deviation for normally distributed parameters or as median and 25th–75th percentiles for non-normally distributed parameters. Continuous data were compared using the t-test or Mann–Whitney U test, while categorical variables were analyzed using the chi-square test or Fisher’s exact test. Multivariate logistic regression analysis was conducted to identify significant indicators, and the receiver operator characteristic (ROC) curve was used to evaluate diagnostic performance. The optimal cut-off values were determined using the Youden index, and consistency between identified indicators and GINA criteria was assessed using the Kappa value. Pearson or Spearman correlation coefficients were used for correlation analyses, with statistical significance set at P < 0.05.
Results
A total of 287 CRSwNP patients were enrolled, including 156 with asthma and 131 without asthma. Among the asthma patients, 23.7% were diagnosed in the Otolaryngology Department. Significant differences in demographic and clinical characteristics were observed between CRSwNP patients with and without comorbid asthma.
Multivariate logistic regression analysis identified FEF50%pred (odds ratio [OR] 0.937, 95% confidence interval [CI] 0.921–0.953, P < 0.001), history of allergic rhinitis (AR) (OR 3.385, 95% CI 1.450–7.900, P = 0.005), blood EOS count (OR 104.149, 95% CI 16.039–676.286, P < 0.001), and serum total IgE levels (OR 1.002, 95% CI 1.000–1.003, P = 0.029) as indicators of asthma comorbidity in CRSwNP patients. The area under the ROC curve (AUC) for these indicators was 0.890, 0.596, 0.733, and 0.694, respectively. The optimal cut-off values for identifying comorbid asthma were FEF50%pred less than 60.2% (Youden Index: 0.621), blood EOS count greater than or equal to 0.35 × 10^9/L (Youden Index: 0.368), and serum total IgE level greater than or equal to 80.2 kU/L (Youden Index: 0.344). FEF50%pred less than 60.2% was the most important indicator of comorbid asthma in CRSwNP patients (β 3.583, OR 35.974, 95% CI 14.788–87.512, P < 0.001), with a sensitivity of 70.5%, specificity of 91.6%, and positive and negative predictive values of 90.0% and 72.3%, respectively. The asthma comorbidity determined with FEF50%pred less than 60.2% was in good consistency with that defined by GINA criteria (Kappa = 0.608, P < 0.001).
The prevalence of SAD and PAL in 93 asthmatics with CRSwNP and 47 asthmatics without CRSwNP showed that both SAD and PAL were significantly higher in asthmatics with CRSwNP (86.0% vs. 48.9%, χ2 = 22.1, P < 0.001; and 36.6% vs. 2.1%, χ2 = 19.7, P < 0.001, respectively). More patients with moderate-severe asthma were found in asthmatics with comorbid CRSwNP (42.0% vs. 23.4%, χ2 = 4.64, P = 0.031).
Further analysis of data from 112 CRSwNP patients with comorbid asthma (43 with PAL and 69 without PAL) found significant differences in age and lung function measurements between asthmatics with and without PAL. Multivariate logistic regression analysis demonstrated that pre-BD FEF50%pred (OR 0.842, 95% CI 0.788–0.899, P < 0.001) was an indicator of PAL in asthmatics with comorbid CRSwNP, with an ROC-AUC of 0.911. Pre-BD FEF50%pred less than 34.4% (Youden Index: 0.672) was the best in identifying PAL, with a sensitivity of 74.4%, specificity of 92.8%, and positive and negative predictive values of 86.8% and 86.5%, respectively. The PAL comorbidity determined with pre-BD FEF50%pred less than 34.4% was in good consistency with that defined by a post-BD FEV1/FVC ratio less than 0.7 (Kappa = 0.69, P < 0.001).
In CRSwNP patients (n = 287), pre-BD FEF50%pred was negatively correlated with blood EOS count (r = –0.255, P < 0.001), blood EOS percentage (r = –0.263, P < 0.001), and serum total IgE level (r = –0.253, P < 0.001), but not with FeNO levels (r = –0.142, P = 0.052). In patients with asthma and comorbid CRSwNP (n = 156), pre-BD FEF50%pred was negatively correlated with age (r = –0.213, P = 0.008) and duration of asthma (r = –0.175, P = 0.029), but not with blood EOS count, blood EOS percentage, serum total IgE level, FeNO level, asthma onset age, or duration of nasal obstruction.
Discussion
The study suggests that decreased FEF50 is a valuable indicator of asthma comorbidity in CRSwNP patients and of PAL in those with comorbid asthma. FEF50%pred less than 60.2% was identified as the most important indicator of comorbid asthma, with high sensitivity and specificity. Pre-BD FEF50%pred less than 34.4% was the best indicator of PAL in asthmatics with comorbid CRSwNP. These findings highlight the importance of monitoring FEF50 in CRSwNP patients with suspected asthma, as it may help in early identification, monitoring, and treatment of comorbid asthma.
The study also found that asthma in CRSwNP patients is more severe than in those without CRSwNP, emphasizing the need for early diagnosis and management. The lack of correlation between FEF50%pred and FeNO levels suggests that non-type 2 (T2) mechanisms may be involved in the development of PAL in asthmatics with CRSwNP.
Conclusion
This study identified decreased FEF50 as a valuable indicator of asthma comorbidity in CRSwNP patients and of PAL in those with comorbid asthma. Monitoring FEF50 may help improve the diagnosis and prognosis of asthmatics with comorbid CRSwNP. However, prospective multicenter studies with larger cohorts are needed to further evaluate the value of FEF50 decline in predicting asthma occurrence and PAL development, as well as guiding anti-inflammatory treatment.
doi.org/10.1097/CM9.0000000000002925
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