INTRODUCTION

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Nasal polyposis (NP) is a frequent chronic rhinosinusitis which is responsible for persistent nasal obstruction and anosmia. NP is characterized by the protrusion of bilateral benign edematous polyps from the meatus into the nasal cavities. The events initiating the formation of nasal polyps remain poorly understood, although eosinophils seem to play a central role in the pathogenesis of NP (1). Treatment of NP consists of medical and/or surgical management. Topical steroid therapy has a well established role in the management of NP, since it has proven efficacy on symptoms and size of polyps and may help prevent the recurrence of NP after surgery (2). Surgical management of NP aims to restore normal nasal function, including nasal ventilation and sinus drainage, when topical steroids alone are insufficient (9).

NP is commonly found in association with lower tract respiratory disorders, such as asthma and bronchial hyperresponsiveness (BHR) (10). The significance of asymptomatic BHR associated with NP is unknown but it may represent an indication of potential asthma. Conflicting opinions exist concerning the evolution of asthma and asymptomatic BHR in patients with NP. The impact of medicosurgical treatment of NP on the evolution of associated asthma and asymptomatic BHR is still controversial (11). Some studies have indicated that polypectomy and sinus surgery may induce worsening of asthma severity (14). In fact, few investigators have evaluated the consequences of sinus surgery in NP relying on objective criteria such as lung volumes measurements and evaluation of BHR with provocation tests. Those who did have reported variable changes in airway reactivity and lung volumes 12 mo after surgical treatment of NP (15). More recently, we reported an enhancement of nonspecific BHR and a significant but modest decrease of FEV₁ over 12 mo in 23 topical steroids nonresponder patients who underwent intranasal ethmoidectomy, whereas no change was observed in 21 topical steroids responders. However, no change in pulmonary symptoms and asthma severity was observed (18).

To date, the long-term outcome of asthma and asymptomatic BHR associated with NP remains to be documented. Therefore we initiated a prospective study to determine the evolution of respiratory symptoms, lung function, and BHR in patients with NP over a period of 4 yr. We investigated whether subjects' characteristics and NP management could contribute to lung function changes in patients with NP.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Patients

We studied 48 patients (31 male, 17 female) consecutively referred to the Calmette Hospital for pulmonary evaluation of noninfectious NP. The mean age (± SEM) was 43.2 ± 2 yr. Nasal polyps were identified in all patients by the following criteria: nasal symptoms (obstruction, anosmia, sneezing, rhinorrhea, itching) and visualization of polyps by anterior rhinoscopy. Each nasal symptom was scored from 0 to 3: 0 for no symptom, 1 for mild symptom (just noticeable), 2 for moderate symptom (annoying), and 3 for severe symptom (distress), so that maximal nasal score was 15 of 15. The extent of polyposis was evaluated with sinus computed tomography (CT) scan; staging of the sinus disease was performed according to the radiological scoring system proposed by Newman and coworkers (19). The area of interest was divided into the nasal cavity, the osteomeatal complex region, and the individual sinuses. Based on the degree of obstruction, 0 to 3 points were awarded for the nasal passages and each of the two osteomeatal complexes. The maximal amount of single wall mucosal thickening in millimeters was measured in each of seven sinus areas (two frontal, two maxillary, two ethmoid, and single sphenoid); each area was awarded 0 to 3 points. Overall score can range from 0 to 33, representing the sum of scores assigned to each area. At the time of inclusion, the patients had not used topical or oral steroid treatment in the 3 mo before study entry. Patients with infectious sinusitis and/or previous history of nasal surgery were excluded from the study. The study protocol was approved by a local ethics committee and informed consent was obtained from all the patients.

Study Design

A prospective follow-up of these subjects with NP was conducted from March 1993 to February 1998 with an initial baseline evaluation followed by two evaluations, respectively 1 (T1) and 4 yr (T2) after initial evaluation. At baseline (T0), clinical nasal score was calculated. At the same time, pulmonary evaluation was performed. Information on typical asthma history and asthma severity was collected. Measurements of lung expiratory volumes and nonspecific BHR by a bronchial carbachol challenge were done. Skin prick tests for common allergens (house dust mite, animal danders, grass pollens, and molds) were performed. Serum total IgE was measured by radioimmunosorbent test (Pharmacia Diagnostics, Uppsala, Sweden).

Then, a standardized treatment was initiated with topical steroids (beclomethasone: 100 µg in each nostril 3 times a day) during a period of 6 wk. After this training period, nasal symptoms were reevaluated. Steroid responsiveness was defined as a decrease of nasal symptoms of more than 4 of 15 after 6 wk topical steroids treatment. If the medical treatment was successful, it was continued. In case of no clinical improvement (topical steroids nonresponders), surgery was undertaken (intranasal ethmoidectomy), followed by an 8-d oral steroid treatment. Topical steroids were associated with surgery. Thus, whether or not surgery was performed, the 48 patients received topical steroids. During the study period, no other medication for NP was allowed.

Forty-six of the 48 subjects were reexamined at T1 and T2, respectively, 12.7 ± 0.9 mo and 47.9 ± 2.2 mo after their baseline evaluation, undergoing the same pulmonary evaluation as in the baseline evaluation. Information on nasal and asthma symptoms was collected (two patients were lost during follow-up; these two patients were responders to topical steroids. They were contacted by phone at T1 and T2: they did not present nasal or respiratory symptoms). In addition, at T2, bronchodilator response was measured at least 48 h after bronchial carbachol challenge as the increase in FEV₁ at 15 min after a 200-µg dose of inhaled salbutamol.

Definitions

Asthma was defined according to the criteria suggested by the American Thoracic Society (20). The asthma severity was assessed according to Aas's scoring system (from score 1 for very mild forms to score 5 for an incapacitating disease) (21). The asthmatic subjects had stable asthma at the time of inclusion and required only intermittent inhaled bronchodilator to control their symptoms. Exclusion criteria for patients with asthma were lower respiratory tract infection in the previous 8 wk, current smoking habit, asthmatic exacerbation in the preceding 8 wk, and treatment with inhaled or oral corticosteroids in the 3 mo before the study. Atopy was defined as the presence of at least one positive skin prick test, i.e., wheal size superior to the one of histamine. BHR was defined by a provocative dose of carbachol causing a 20% fall in FEV₁ from baseline values (PD₂₀)  1,280 µg (22). Carbachol responses were subcategorized into six response ranges based on the following threshold values: > 1,280, 960 to 1,280, 640 to 960, 320 to 640, 160 to 320,  160 µg. BHR was considered to be worsened in case of an increase in PD₂₀ carbachol of two categories and improved in case of a decrease in PD₂₀ carbachol of two categories at T1 or T2.

Surgical Procedure

The surgical technique consisted of a microscopical intranasal sphenoethmoidectomy (23). Surgery was performed under general anesthesia. Surgical microscopical procedure included first the resection of the anterior part of the middle turbinate. After removal of the inferior border and the tail of the middle turbinate, the posterior ethmoid was entered as well as the sphenoidal sinus. Polyps and septi were removed and a complete ethmoidectomy and a wide sphenoidotomy were performed. The exenteration of the entire ethmoid labyrinth was completed, working anteriorly along the fovea ethmoidalis, for maximal removal of the disease. If there was a significant deviation of the nasal septum, it was corrected to improve exposure of the middle meatus. Intranasal antrostomy was performed in the inferior meatus for drainage of any retained mucus or blood. A supplemental antrostomy might be made supraturbinally in the middle meatus. Frontal sinuses were not manipulated.

Pulmonary Function Tests and Carbachol Inhalation Challenge

All measurements were made in the sitting position. Forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and maximal midexpiratory flow (FEF_25-75) were obtained from flow-volume curves using a Medgraphics spirometer (St. Paul, MN). The largest values of FVC, FEV₁, and FEF_25-75 from the first three technically satisfactory forced expirations were selected (24). All data were expressed in absolute values and in percentage of predicted normal values. Bronchial provocation tests were performed according to the guidelines of the European Society for Clinical Respiratory Physiology (25). Carbachol challenges were performed sequentially with a Mediprom dosimeter (Paris). The latter is derived from the Rosenthal-French dosimeter (Johns Hopkins University, Baltimore, MD) in which the opening of a solenoid valve is triggered by the patient's inhaling. The dosimeter makes it possible to preset the delivery time, the pause between deliveries, and the number of breaths. In our laboratory, we selected a delivery time of 0.6 s and a pause between deliveries of 10 s. We used a carbachol solution (10 mg/ml) prepared with carbachol powder (Sigma Chemical Co., St. Louis, MO) diluted with saline. Patients inhaled from functional residual capacity to total lung capacity, first saline solution followed by doubling doses of carbachol, starting from 160 µg. The procedure was ended when FEV₁ decreased by 20% or when a cumulative dose of 1,280 µg of carbachol was reached. Measurements were performed 2 min after each step. Doses were given at 5-min intervals, completion of all measurements lasting 25 min for each patient. Dose-response curves were constructed by plotting FEV₁ against increasing doses of carbachol. PD₂₀ was determined by interpolation from the dose-response curve. Asthmatic patients using inhaled ₂-agonists had to stop their medication 12 h before the carbachol challenge was performed.

Statistical Evaluation

The statistical analysis was performed with a Macintosh computer (Apple Company, Cupertino, CA) using the Statview 5.0 Software (Statview, Inc.). Applicable data were expressed as mean ± SEM. For continuous variables, Student unpaired t test was used to compare mean values of the items with standard normal distributions between topical steroids nonresponders and topical steroids responders. Categorical variables were analyzed with Fisher exact test. Repeated-measures analysis of variance (ANOVA) was performed for the pooled data (T0, T1, and T2), with time as within factor, group (steroids nonresponders/steroids responders) as between factor, and an interaction between time and group. Then, repeated-measures ANOVA was used for within-groups comparisons (factor time). When a significant F test was obtained, Student's paired t tests were carried out. BHR was expressed as the continuous variables 1 to 6 for the PD₂₀ thresholds: > 1,280, 1,280 to 960, 960 to 640, 640 to 320, 320 to 160, 160 µg. As BHR was not normally distributed, the Mann-Whitney U test for unpaired comparisons and the Wilcoxon test for paired comparisons were used. ANOVA was used to assess the relationships of FEV₁ changes between T2 and T0 as dependent variable with the following independent variables: BHR (presence or absence), asthma (presence or absence), and atopy (yes or no). For each test, a p value less than 0.05 was considered statistically significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Baseline Characteristics

Characteristics of the 46 patients at baseline evaluation (T0) are summarized in Table 1. Twenty-five patients (54%) exhibited nonspecific BHR. Among them, asthma history was clearly identified in 16 patients (35%) and 11 of 16 had aspirin-sensitive asthma. One patient had aspirin intolerance without asthma. Five asthmatics were atopic. Severity of asthma was mild; asthmatic patients were classified by Aas score 1 (n = 12) and 2 (n = 4). None were receiving inhaled steroids for asthma for 3 mo before inclusion. Mean nasal score was 8.3 ± 0.3. Mean duration of nasal symptoms was 8.0 ± 1.9 yr. Twenty-two patients received one or two courses of antibiotics in the year prior to the inclusion.

After 6 wk of topical steroid treatment (beclomethasone 600 µg/d), according to clinical findings, two groups were identified: 28 patients did not respond to topical steroid treatment and underwent intranasal ethmoidectomy (topical steroids nonresponders), and 18 patients responded to topical steroids (topical steroids responders) (Table 1). The two groups were not different in regard to age, total IgE, prevalence of nonspecific BHR, asthma, ASA intolerance, and atopy. Mean duration of nasal symptoms, nasal scores, and radiological scores did not differ between the two groups.

Nasal Score Evolution

After 6 wk of topical steroid treatment, nasal score significantly decreased in responders whereas it remained unchanged in nonresponders (Table 2). Within-groups analysis showed a significant decrease in nasal score in both groups at T1 (p < 0.0005). Nasal score remained improved at T2 in both groups, as compared with T0, although it moderately increased at T2 as compared with T1 in steroids nonresponders (p < 0.05). Between-groups analysis showed that nasal scores were not statistically different between the two groups at T1 and T2. At T1, all patients (n = 46) were treated with the same dosage of topical steroids (beclomethasone 600 µg/d). Between T1 and T2, topical steroids treatment observance similarly decreased in the two groups. Twelve steroids nonresponders and seven steroids responders discontinued topical steroids treatment between T1 and T2. The remaining patients were treated with the same dosage of topical steroids (beclomethasone 600 µg/d).

Pulmonary Function Evolution

At baseline, there was no significant difference in pulmonary function between the two groups (Table 1). Within-groups analysis showed a significant decrease in FEV₁, FEV₁/FVC ratio, and FEF_25-75 at T1 compared with T0 in nonresponders (Table 3). At T2, FEV₁, FEV₁/FVC ratio, and FEF_25-75 were significantly decreased compared with T0 in nonresponders. In addition, FEV₁ (ml) was significantly lower at T2 than at T1 in nonresponders. By contrast, no significant change was observed in responders at T1. At T2, FEV₁ and FEV₁/FVC ratio remained stable. FEF_25-75 moderately decreased at T2 compared with T1 in steroids responders. Between-groups analysis showed that FEV₁ (%) was significantly lower at T2 in steroids nonresponders than in steroids responders. Over the 4-yr follow-up period, the reduction in FEV₁ (%) was higher in nonresponders (8.8 ± 1.2%) than in responders (0.7 ± 2.6%). The same trend was observed for FEV₁/FVC ratio (Figure 1). FEV₁ decrease ranged from 200 to 400 ml in 11 of 28 nonresponders and in only two of 18 responders; FEV₁ decrease exceeded 400 ml over the 4-yr follow-up period in 13 nonresponders and in only one responder. At T2, bronchodilator response was similar in nonresponders (n = 24) and in responders (n = 13) (percent change in FEV₁: 6.6 ± 1.5% versus 5.1 ± 1.6) (p = 0.54). Mean increase in FEV₁ after bronchodilator was similar in the two groups (161 ± 33 ml versus 165 ± 60 ml) (p = 0.96).

View larger version (26K): [in this window] [in a new window]   Figure 1.   Changes in lung function in patients with NP after 4-yr follow-up. T0 = initial evaluation; T2 = third evaluation (mean time after T0 = 47.9 ± 2.2 mo). *p Value of unpaired Student's t test analysis between steroid nonresponders and steroid responders.

At T0, subjects with BHR exhibited a lower FEV₁ and FEF_25-75 than subjects without BHR (p < 0.01). FEV₁ (%) significantly decreased at T2 compared with T0 in subjects with BHR (respectively, 98.3 ± 13.0% at T0 and 94.3 ± 13.4% at T2) (p < 0.05) and in subjects without BHR (113.3 ± 20.0% and 103.2 ± 15.7%) (p < 0.01). FEV₁/FVC ratio also decreased in both groups at T2 as compared with T0 (p < 0.05).

FEV₁ and FEF_25-75 were significantly lower at T0 in asthmatics as compared with nonasthmatics (p < 0.05). A significant decrease of FEV₁ and FEV₁/FVC ratio was observed in asthmatic nonresponders as well as in nonasthmatic nonresponders whereas these parameters remained stable in asthmatic responders and in nonasthmatic responders (Figure 2). Bronchodilator response at T2 was higher in asthmatics than in nonasthmatics (Table 4). Bronchodilator response was larger than 12% and exceeded 200 ml in four asthmatics (two nonresponders and two responders). Within asthmatics and nonasthmatics, bronchodilator response was similar in responders and in nonresponders. FEV₁ (%) between T2 and T0 did not correlate with the existence of asthma (F test = 0.75; p = 0.38), or BHR (F test = 2.75; p = 0.15) or atopy (F test = 0.06; p = 0.79).

View larger version (20K): [in this window] [in a new window]   Figure 2.   Changes in FEV1 and FEV1/FVC ratio in asthmatics and nonasthmatics. Values are expressed as mean ± SEM. T0 = initial evaluation; T1 = second evaluation (mean time after T0 = 12.7 ± 0.9 mo); T2 = third evaluation (mean time after T0 = 47.9 ± 2.2 mo). *p < 0.05, unpaired Student's t test analysis between asthmatics and nonasthmatics in nonresponders. Multivariate repeated-measures analysis of variance (MANOVA) for within-groups comparisons:  p < 0.005, significantly different from T0;  p < 0.05, significantly different from T0.

BHR Evolution

At baseline values, among patients who exhibited nonspecific BHR, mean PD₂₀ was similar in the two groups (Table 1). No significant change of mean BHR occurred in topical steroids nonresponders and in topical steroids responders between T0 and T1, between T0 and T2, and between T1 and T2. Between-group comparisons did not show significant difference in BHR between the two groups at T1 and at T2. In addition, BHR remained stable in asthmatics and in nonasthmatics. When considering a significant change of BHR as a decrease or an increase in PD₂₀ of at least two categories, BHR remained stable in 18 of 28 steroids nonresponders and in 12 of 18 steroids responders over the follow-up period. The number of patients with increased BHR at T1 tended to be higher in steroids nonresponders (n = 4) than in steroids responders (n = 1) but the difference did not reach statistical significance (Table 5). Number of patients with improved BHR or stable BHR at T1 was similar in the two groups. Between T1 and T2, in steroids nonresponders, BHR returned to baseline values in the four patients with increased BHR at T1, whereas it worsened in two other patients. In steroids responders, BHR remained worsened in one patient, worsened in one other, and improved in three. Thus, at T2, the number of patients with improved, worsened, or stable BHR at T2 as compared with T0 did not differ between the two groups.

Asthma Severity

Asthma severity, according to the Aas scoring system, did not significantly vary during follow-up in the two groups. In steroids nonresponders, six asthmatics remained stable as judged by the same Aas score during follow-up. Three asthmatics demonstrated a moderate worsening of their asthma requiring inhaled steroids between T1 and T2 as suggested by the increase in the Aas score (from 1 to 2 for two patients, from 1 to 3 for one), whereas one asthmatic exhibited a clinical improvement (decrease of the Aas score from 2 to 1). One steroids nonresponder who exhibited asymptomatic BHR at T0 noticed the appearance of episodic wheezings requiring inhaled steroids and ₂-agonists at T2. The remaining nonresponders (n = 15) did not experience discernible changes. In the steroids responders group, five asthmatics remained stable and one demonstrated a worsening of asthma severity requiring inhaled steroids (increase of the Aas score from 1 to 3). One patient without BHR at T0 experienced the appearance of symptomatic BHR at T2 requiring inhaled steroids. The remaining responders (n = 11) remained stable during follow-up. At T0 and T1, none was receiving inhaled steroids. Between T1 and T2, inhaled steroids were started in six nonresponders (five asthmatics and one without BHR at T0) and in three responders (two asthmatics and one without BHR at T0).

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The present study shows that subjects with NP who did not respond to topical steroids and required nasal surgery exhibited a significant decrease of FEV₁ and FEV₁/FVC ratio over a 4-yr period, whereas these parameters remained unchanged in subjects with NP who responded to topical steroids. These changes were not related to the presence of nonspecific BHR and/or asthma. In addition, the occurrence of that nonreversible airflow obstruction in steroids nonresponders was not associated with significant changes in asthma severity or with the appearance of asthma symptoms. In the same time, no significant change in nonspecific BHR was observed in the two groups of patients with NP.

There are two conflicting opinions that have been expressed in numerous previous publications concerning the effects of sinus surgery for NP on asthma and/or nonspecific BHR. Some studies stated that sinus surgery may initiate or worsen asthma, others advocated that surgical treatment for NP will assist in the management of associated asthma (9). It is difficult to evaluate the true effect of sinus surgery because most of the studies relied on the analysis of subjective criteria (frequency of asthma attacks, perception of wheezing, global control of asthma) or on the evaluation of medical needs to control asthma (including oral steroids which are also administered to improve nasal symptoms before sinus surgery becomes necessary). In fact, the objective consequences of sinus surgery for NP have been analyzed in few studies, which provide controversial conclusions. Jankowski reported an increased number of subjects with "normal" FEV₁ 12 mo after ethmoidectomy and the disappearance of nonspecific BHR in more than 30% of cases among 30 subjects with NP and asthma (15). Vleming also showed an improvement of pulmonary function tests after sinus surgery in 64% of 30 asthmatics with NP (17). On the other hand, Korchia reported a loss of 200 ml or more in FEV₁ in five patients, no change in three patients, and an improvement in three patients 12 mo after ethmoidectomy (16). Nevertheless, the conclusions of these studies are severely weakened by the fact that they include many biases. Diagnosis criteria and treatment for asthma at inclusion are not specified; the exact values of lung function parameters and criteria of normal lung values are not given. Finally, only asthmatics with NP who underwent sinus surgery were evaluated in these studies; subjects with NP without BHR and/or asthma receiving medical treatment were not included. Thus, the authors cannot exclude the hypothesis that their findings resulted from the natural evolution of asthma rather than from sinus surgery. Some criticisms may also be raised concerning the present study. First, the definition of steroid-responsiveness in patients with NP is controversial. We considered that subjects were nonresponsive as long as they did not improve nasal symptoms after a 6-wk nasal steroid treatment. The duration of nasal steroid therapy is often longer in the literature. Nevertheless, the efficacy of nasal steroids is observed right from 4-wk topical steroid therapy in most cases, suggesting that steroid-responsiveness may be evaluated after 6 wk (2). The small size of the sample we studied and the limited duration of the follow-up represent other limitations of this study. Despite these limitations, this study may provide worthwhile information because statistical analysis evidenced striking differences between nonresponders and responders.

Except for the studies which aimed to assess the effects of nasal surgery, there is a remarkable lack of studies dealing with the short-term and long-term evolution of lung function after medical treatment for NP. We recently investigated the changes in lung function and nonspecific BHR over 12 mo in 44 patients with NP treated either with topical steroids alone (steroids responders) or with topical steroids associated with intranasal ethmoidectomy (steroids nonresponders) (18). We reported an enhancement of nonspecific BHR and a modest but significant decrease in FEV₁ and FEF_25-75 in steroids nonresponders, whereas these parameters remained stable in steroids responders. However, no obvious change in pulmonary symptoms and in asthma severity occurred. Despite the appearance of a slight airflow obstruction, our results clearly evidenced that sinus surgery for NP was not associated with an obvious improvement or worsening of asthma at 12 mo. The present study partly confirmed our previous findings. The decline of FEV₁ and FEV₁/FVC ratio at 12 mo was sustained over the 4-yr follow-up period in steroids nonresponders, whereas nonspecific BHR remained stable in nonresponders and in responders.

The mechanisms by which airflow obstruction occurs in subjects with NP who do not respond to topical steroids remain questionable. One can hypothesize that nonspecific BHR may participate in FEV₁ decline because longitudinal studies have shown a faster decline of pulmonary function in subjects with BHR compared with subjects without BHR (26, 27). In our study, nonspecific BHR may be responsible for a lower FEV₁ and FEV₁/FVC ratio in subjects with BHR. However, FEV₁ decline over the 4 yr may not be solely attributable to the existence of nonspecific BHR because it was reported whether or not BHR existed in steroids nonresponders and was not observed in steroids responders with BHR. In addition, the evolution of nonspecific BHR was similar in the two groups after 4 yr, showing a high intraindividual variability of BHR levels in subjects with preexisting BHR. Lastly, no difference in bronchodilator response could be demonstrated between the two groups, suggesting that airway obstruction which occurs in nonresponders is distinct from asthma. Preferential mouth breathing secondary to nasal obstruction has been proposed to explain the relationship between chronic nasal diseases and lower respiratory tract disorders (28). Although it tended to worsen at 4 yr in steroids nonresponders, clinical nasal score (which included the assessement of nasal obstruction) improved in the same way in the two groups at 1 and 4 yr in comparison with initial evaluation, suggesting that mouth breathing does not account for the occurrence of airflow obstruction in nonresponders.

Finally, it can be hypothesized that FEV₁ decrease results either from intranasal ethmoidectomy per se or from a topical steroid-nonresponsive nasal disease which may progressively involve the lower respiratory tract. Indeed, another proposed mechanism connecting upper and lower airways diseases is the production of inflammatory mediators that could either be aspirated into the lower airways or locally stimulate irritant receptors in the sinuses with resultant nasobronchial reflex (28, 29). Nasal polyps are known to exhibit several inflammatory features, including increased number of eosinophils, mixed mononuclear cells, and large amount of inflammatory mediators such as cytokines, adhesion molecules, and transcription factors (30). Because steroid nonresponsive state was shown to be associated with persistent expression for inflammatory cytokines (33, 34), one cannot exclude that pulmonary aspiration of nasal inflammatory contents in steroids nonresponders might contribute to the occurrence of lung alterations. Another hypothesis is that intranasal ethmoidectomy per se would lead to the release of inflammatory mediators. The fact that both responders and nonresponders had similar lung volume values at inclusion is of crucial importance. Indeed, one would expect that initial cross-sectional level would predict rate of change. The fact that lung volume values of nonresponders were quite close to responders' values supports the hypothesis that the accelerated decline in lung function in nonresponders is linked to nasal surgery rather than to a topical steroid-nonresponsive nasal disease.

In conclusion, steroids-nonresponsive NP treated by nasal surgery is associated with progressive FEV₁ decline and appearance of airflow obstruction 4 yr after intranasal ethmoidectomy, regardless of the existence of nonspecific BHR. Pulmonary prognosis in steroid-responsive NP appears to be favorable, because subjects with NP who improved on topical steroids exhibited a remarkable stability of lung function over time whereas steroid-nonresponsive NP may be regarded as a risk factor for chronic obstructive airways disease, the exact nature and evolution of which remain to be determined.