Abstract
This study aimed to investigate the effect of chronic rhinosinusitis/nasal polyposis on the severity of COPD and to find out whether the ‘united airway disease’ hypothesis is valid for COPD. The study enrolled 90 patients diagnosed and staged according to criteria of an international guideline for diagnosis and management of COPD. The patients in stages I and II were classified as Group 1 and the patients in stages III and IV as Group 2. All the patients were questioned about the presence of major and minor criteria of sinusitis, underwent paranasal sinus computed tomography (PNS-CT) scans, and answered a questionnaire based on a quality of life test for sinusitis (SNOT-20). Sinusitis was present in 48 (53%) patients according to criteria of major and minor symptoms, and in 58 (64%) patients according to Lund-Mackay scoring system of PNS-CT. There was no significant difference in CT score between Group 1 and Group 2 (2.3 ± 0.5 vs. 2.1 ± 0.4, p > 0.05). However, the frequency of minor symptoms was greater in Group 2. SNOT-20 score was significantly higher in Group 2 than in Group 1 (28.7 ± 1.7 and 22.2 ± 1.9, respectively, p = 0.014). A significant correlation was determined between Lund-Mackay and SNOT-20 scores. The presence of CRS should be assessed in COPD patients, especially in those with severe disease. Further research is needed to disclose possible common immunopathological mechanisms in the pathogeneses of COPD and CRS.
Keywords: :
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a respiratory disease that is not fully reversible and is a systemic disorder that may be accompanied by weight loss, muscle weakness, decreased functional capacity, anemia and osteoporosis. The severity of the disease is defined by spirometric measurements (Citation1).
Rhinosinusitis is a pathological process depending on concomitant inflammation of nasal mucosa and paranasal sinuses (Citation2). “European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)”, a widely recognized guideline for the diagnosis and management of chronic sinusitis and nasal polyposis, defines rhinosinusitis by the presence of at least two symptoms indicating inflammation in the nose and sinuses in addition to the presence of endoscopic findings and/or paranasal sinus computed tomography (PNS-CT) findings (Citation3).
Previous studies suggested correlations between endoscopic findings and significant CT changes (Citation4, 5). PNS-CT is the gold standard technique to evaluate the paranasal sinuses (Citation6). CRS in adults is defined by the presence of at least two major or one major and two minor symptoms (Citation7).
Coexistence of lower airway diseases and rhinosinusitis
Epidemiologic and physiological studies demonstrate that lower and upper airway diseases often coexist. The association between allergic rhinitis and asthma is explained by the “united airway disease” hypothesis (Citation8). An association between upper and lower airways is suggested in COPD as well (Citation9, 10).
It is generally recognized that rhinitis accompanies about 90% of asthma cases and that asthma develops in about one third of patients with allergic rhinitis. Furthermore, rhinitis patients have three times more risk to develop asthma throughout their life (Citation8). Recent studies reported high prevalence rates of sinonasal symptoms in COPD, ranging between 75% and 88% (Citation11, 12). Nasal symptoms that were most frequently reported in these studies were nasal discharge, nasal obstruction, and sneezing.
The conditions leading to nasal obstruction may trigger lower airway disorders. Nasal polyps may result in total blockage of nasal passage in chronic rhinosinusitis patients (Citation13). Activation of nasal neutrophils and capacity of producing secretory response to histamine were found to be increased in cases with COPD and nasal complaints, compared to cases with COPD alone. Nasal IL-8 was shown to be higher in COPD patients and this increase was correlated with the increase in IL-8 level and bacterial load in sputum (Citation14–18).
This study aimed to investigate the impact of the presence of chronic rhinosinusitis/nasal polyposis in COPD patients on the severity of the disease and to find out whether the ‘united airway disease’ hypothesis is valid for COPD.
MATERIAL AND METHODS
Cumhuriyet University Faculty of Medicine Local Ethics Committee approved the study and all patients provided written informed consent.
Patients
This study enrolled 90 consecutive patients who attended the outpatient clinic of chest diseases in Cumhuriyet University Hospital, who were diagnosed as COPD according to GOLD criteria (Citation1), and who accepted to participate in the study.
The patients were questioned about occupation, smoking, duration of COPD symptoms, time span since COPD diagnosis by a doctor, routinely used medications, numbers of hospitalization and admission to intensive care unit during the last year, use of BiPAP, use of long-term oxygen therapy, previous diagnosis of sinusitis and/or nasal polyposis, previous operation for nasal polyp, and previous treatment for sinusitis.
Diagnosis and staging of COPD
The patients were staged according to GOLD criteria. Stages I and II were classified as Group 1, and stages III and IV as Group 2.
Pulmonary function tests were executed using a flow-sensitive spirometer (VMax 20C, SensorMedics, Yorba Linda, California, USA). During a clinically stable period, patients performed the forced vital capacity maneuver at least three times, in sitting position. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FVC/FEV1) were measured. Best absolute (in milliliters) and percentage (of predicted) values were recorded. The predicted values were those of “ERS 1993 update”.
Assessment of sinusitis
For the clinical diagnosis of sinusitis, major and minor criteria proposed by the International Rhinosinusitis Advisory Board were applied. Major symptoms were facial pain/pres- sure/fullness, nasal obstruction/blockage, nasal or post-nasal discharge/purulence, and hyposmia/anosmia. Minor symptoms included headache, ear pain/pressure/fullness, halitosis, and fatigue (Citation7).
The patients answered a questionnaire adapted from Sinonasal Outcome Test-20 (SNOT-20), a twenty-item quality of life questionnaire specific to sinonasal disorders such as rhinosinusitis and nasal polyposis (Table 3). The questionnaire was evaluated using the arithmetic mean of total score. Furthermore, SNOT-20 questionnaire was divided into subsets based on a study by Browne et al. (Citation19). The first subset was composed of the questions about the symptoms related to nose, ear, and face; the second subset included the questions on psychological issues; and the third subset addressed sleep function. SNOT-20 scores were further evaluated for these three subsets separately.
Paranasal sinus computed tomography (PNS-CT)
The PNS-CT scans of the subjects were obtained using a Philips Brilliance 16-slice CT scanner. In order to examine radiographically in the coronal plane, the patients were positioned face-down with the chin elevated. After obtaining the scout projection, the area of scanning was defined to include the region from anterior wall of frontal sinus up to posterior wall of sphenoid sinus. The sections were taken with slice thickness of 3 mm, scanning parameters being 120 kVp and 400 mAs. No contrast material was used.
CT images were scored according to Lund-Mackay system proposed by American Academy of Otolaryngology Task Force on Rhinosinusitis for the radiological evaluation of CRS. This scoring system gave 0 point for no opacification, 1 point for partial opacification, and 2 points for total opacification in each sinus. The ostiomeatal complex was scored as 0 if not occluded or 2 if occluded (Citation20). Since the Lund-Mackay radiological scoring system had no specific cut-off value, the minimal possible score 0 was considered as normal or negative, and any score greater than 0 was considered as abnormal or positive (Citation21).
Statistical analysis
For the statistical analyses, SPSS 13.0 (Statistical Package for Social Sciences, for Windows, USA) program was utilized. The mean values were expressed as mean ± SEM. Means of independent groups were compared with Student's t-test; nominal variables were compared with chi square test. The correlations between the means of independent groups were evaluated with Pearson correlation test. A p value < 0.05 was considered as significant. Confidence interval was defined as 95%.
RESULTS
Of the 90 patients included, more than two-thirds were male. exhibits some of the demographical and clinical features of the patients. Groups 1 and 2 did not differ significantly in the rates of previous diagnosis of sinusitis, previous diagnosis of nasal polyposis, and previous treatment for sinusitis (p > 0.05).
Table 1 Demographical and clinical features of the patients (n = 90)
There was no significant difference between two groups regarding the number of major criteria (p > 0.05). On the contrary, the average number of minor criteria was higher in Group 2, compared to that in Group 1 (p = 0.02). When the groups were compared for individual sinusitis symptoms, fatigue was found to be more frequent in Group 2 (p = 0.02); none of the other symptoms produced any statistically significant difference ().
Table 2 Frequencies of diagnostic symptoms of sinusitis within Group 1 and Group 2
When the genders were compared, facial fullness was more frequent in female patients (p = 0.03).
The rates of the patients who were diagnosed as sinusitis according to symptomatic criteria were statistically similar in Group 1 and Group 2 (47.2% and 57.4%, respectively, p > 0.05). Similarly, the rates of patients who had two major criteria, one major and two minor criteria or none of the criteria did not differ between Group 1 and Group 2 (p > 0.05).
As for the results of SNOT-20 questionnaire, the average total point was 26.1 ± 1.3 for all. It was 22.2 ± 1.9 in Group 1 and 28.7 ± 1.7 in Group 2, establishing a significant difference (p = 0.014). Correspondingly, the average score of SNOT-20 was 1.3 ± 0.1 for all. It was 1.1 ± 0.1 in Group 1 and 1.4 ± 0.1 in Group 2, substantiating again a significant difference (p = 0.013). There was no significant difference between male and female patients (p > 0.05).
In the subset analysis of SNOT-20 questionnaire, the subsets concerning psychological issues and sleep function were found to produce significantly higher scores in Group 2 than in Group 1 (9.6 ± 0.9 vs. 6.3 ± 1.0, p = 0.013 and 4.9 ± 0.7 vs. 4.3 ± 0.7, p = 0.029; respectively). The levels of difficulty falling asleep, waking up at night, lack of a good night's sleep, fatigue, and reduced productivity were significantly higher in Group 2 ().
According to the presence of major and minor symptomatic criteria, 48 patients (53.3%) had sinusitis. These patients with sinusitis had higher scores than those without sinusitis for waking up at night, lack of a good night's sleep, and waking up tired (p = 0.038, p = 0.035, and p = 0.003, respectively). Total SNOT-sleep score was also higher in the group with sinusitis (p = 0.026). As for the parameters within SNOT subset related to nose, ear and face symptoms (SNOT-nose), the patients with sinusitis had higher scores compared to those without (12.93 ± 0.70 vs. 5.50 ± 0.42, p = 0.001). As for the parameters about psychological factors, the patients with sinusitis expressed higher scores for fatigue and being embarrased (p = 0.02 and p = 0.001, respectively). Total SNOT-psychology score was correspondingly higher in the patients with sinusitis (p = 0.003) (). The average total SNOT-20 questionnaire scores were 32.18 ± 1.54 in the patients with sinusitis and 19.07 ± 1.51 in those without sinusitis (p = 0.001).
Table 3 Comparison of SNOT*−20 questionnaire scores in Group 1 and Group 2
Table 4 Comparison of scores of the SNOT-20 subset related to psychological factors between patients with and without sinusitis
The mean PNS-CT score was 2.2 ± 0.3 in total study population, 2.3 ± 0.5 in Group 1, and 2.1 ± 0.4 in Group 2 (p > 0.05). When a gender comparison was made, it was observed that the mean scores in female and male patientas were 1.4 ± 0.4 and 2.5 ± 0.4, respectively. This was a statistically significant difference (p = 0.035).
When a cut-off value of 4 was considered for PNS-CT scores, no significant difference was observed between both groups or between male and female patients. Sinusitis diagnosis established according to major and minor criteria showed no significant correlation with PNS-CT scores (r = 0.16, p = 0.13). A significant but negligibly weak correlation was observed between average SNOT-20 questionnaire scores and PNS-CT scores (r = 0.22, p = 0.04). In Group 2, there was a significant and a little stronger correlation between the SNOT-nose and PNS-CT scores (r = 0.36, p = 0.01); this correlation was insignificant in Group 1 (r = 0.39, p = 0.08).
DISCUSSION
A literature search did not provide any data on the prevalance of the coexistence of COPD and CRS in Turkey. The primary goal of this study was to demonstrate such a coexistence.
In Western countries, CRS was reported to affect almost 15% of the adult population (Citation22). Montnemery et al. applied a questionnaire to a random sample of 8,469 adults in Southern Sweden and determined that 40% of the patients with chronic bronchitis or emphysema and 33% of the general population had nasal symptoms (Citation23). The frequency of sinonasal symptoms in COPD was reported to be as high as 75–88% (Citation11, 12). Of 90 patients enrolled in this study, 48 (53%) had sinusitis according to major and minor symptoms; 58 (64%) manifested sinusitis according to Lund-Mackay scoring system for PNS-CT. Only 20% of the patients included in this study revealed sinusitis history. This rate indicated that COPD patients were not questioned enough about sinusitis. Furthermore, considering the prevalence reported in current literature, this study demonstrated that the frequency of sinusitis in COPD patients was higher than that in general population.
In this study, it was found that 47% of the patients with mild-moderate COPD and 57% of the patients with severe-very severe COPD had sinusitis according to the presence of major and minor criteria. When Lund-Mackay scores of PNS-CT scans were considered, there rates increased to 66% in the former group and to 62% in the latter group. These findings displayed that sinusitis symptoms were clinically more prominent in patients with graver COPD, but there was no difference between severity groups in radiological data. In this study, the average number of minor symptomatic criteria for sinusitis was higher in patients with severe-very severe COPD, compared to those with mild-moderate disease. The authors suggest that this might be related to high frequencies of symptoms like headache, facial fullness, fatigue, and cough in severe COPD patients without sinusitis as well.
For the radiological staging of CRS, the authors utilized the Lund-Mackay scoring system which showed the severity of the disease (Citation24). The average PNS-CT score in this study was 2.2 ± 0.3 and no significant difference was observed between the groups separated by the severity of COPD. On the other hand, there was a significant gender difference to the disadvantage of men. The minimum score for endoscopic sinus surgery in CRS was proposed to be four (Citation25). In this study, the rate of the patients with a Lund-Mackay score equal to or higher than four was 14%. This rate was 16% in the group with mild-moderate COPD and 12% in the group with severe-very severe COPD.
Hwang et al. observed that among 115 patients diagnosed as CRS according to the presence of relevant symptoms, 40 had normal PNS-CT scans. They found that questioning symptoms had a sensitivity of 89% and a specificity of 2% (Citation21). Arango and Kountakis questioned 53 patients about major and minor symptoms of CRS with the use of a visual analogue scale from 0 to 10. Subsequently, the patients underwent PNS-CT scans of which 27 had positive and 26 had negative results. The average scores for major and minor symptoms were respectively 18.6 and 15.0 in patients with negative result of PNS-CT, but 42.9 and 22.0 in patients with positive results of PNS-CT. They reported that the symptom scores were significantly higher in the group with positive radiological findings, but symptom scores and Lund-Mackay scores showed no significant correlation (Citation26). Similarly, the diagnosis of sinusitis according to the presence of major and minor criteria displayed no correlation with PNS-CT scores in this study as well. Out of 48 patients who were diagnosed as sinusitis according to symptom scores, 10 (20.8%) had a PNS-CT score of zero.
In sinonasal diseases such as rhinosinusitis and nasal polyposis, SNOT provides a measurement based on self-reports of the patients. In a study of 102 patients by Piccirillo et al., SNOT was demonstrated to be reliable and valid. It was shown that the patients who were more disturbed due to sinonasal disease had significantly higher scores than those who were less uncomfortable (Citation27). Hurst et al. conducted a study including 65 patients with moderate COPD and observed that 88% of the subjects had nasal symptoms in most days of the week.
The average SNOT-20 score in their patients was 1.24 and they showed that nasal symptoms caused impairment of the quality of life. They identified a significant correlation between SNOT-20 score and daily frequency of nasal symptoms (Citation12). This study, likewise, found that SNOT-20 scores were higher in COPD patients with sinonasal symptoms than in those without. The average total SNOT-20 score was 1.3 ± 0.1 in accord with the literature. When the two study groups were compared, the patients with severe-very severe COPD had significantly higher SNOT-20 scores than those with mild-moderate disease.
When the SNOT questionnaire was divided into subsets as recommended by Browne et al. (Citation19), the subsets containing the questions about psychological issues and sleep function yielded higher scores in the group including the patients with severe-very severe COPD. The subset containing the questions related to nose, ear and face elicited no difference between the study groups. This discrepancy between the subsets was attributed to the presence of psychological and sleep-related disturbances in patients suffering from severe COPD. Like the total SNOT-20 scores, the scores of the subsets were significantly higher in patients with symptomatic sinusitis. This finding supported previous reliability studies of SNOT-20.
Zheng et al. conducted a study enrolling 121 rhinosinusitis patients and demonstrated a weak but significant correlation between SNOT-20 and Lund-Mackay scores (Citation28). This study, similarly, found a very weak but significant correlation between questionnaire and radiology scores.
This study had some limitations. Firstly, the current literature had no data about the prevalence of CRS in the city where this study was conducted; therefore, it was not possible to compare the prevalence in COPD patients with general population living in the same city. For this comparison, the numbers from available literature were used. Secondly, this study lacked laboratory investigations that might indicate a possible immunopathological mechanism common to CRS and COPD, as in the case with asthma. The connection between COPD and CRS could result from the simultaneous irritation of the lower and upper airways by exhaling tobacco smoke through the nose. Such an association could be demonstrated by the investigation of inflammatory cells and markers and the examination of tissue samples throughout the affected portions of the respiratory mucosa.
In conclusion, this study showed that COPD and CRS coexisted frequently. The symptoms of sinusitis might be attributed to the systemic reflection of the inflammatory process in COPD. However, there was no difference in the prevalence of sinusitis between mild-moderate and severe-very severe COPD patients. On the other hand, symptoms such as fatigue, weakness, sleeplessness, and waking up tired are common among COPD patients especially in advanced stage. These symptoms lead to impaired quality of life in rhinosinusitis as well. The presence of these symptoms in COPD patients should alert the physician to investigate a possible underlying sinonasal disease. Further research is needed to disclose the immunopathological mechanism(s) resulting in the co-occurrence of COPD and CRS.
DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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