Increased airway inflammation in patients with psoriasis

Dear Editor, Psoriasis, currently the most common dermatitis, is considered a systemic chronic inflammatory disease with an unclear pathogenesis.1 In the literature, psoriasis has been demonstrated to increase the incidence of a large number of diseases that share an inflammatory origin.2 While several hypotheses have been proposed, the currently most accepted is that of proinflammatory cytokine spillover from active psoriatic lesions, which may cause inflammation in distant tissues.1 Recently, increased tissue positivity to several proinflammatory cytokines, including tumour necrosis factor‐α, has been observed in psoriasis plaques and blood.3 This cytokine is able to develop and maintain inflammation by increasing the transcription of several enzymes, such as the inducible form of nitric oxide synthase (iNOS),4 which synthesizes nitric oxide (NO) from arginine,4 and arginase. However, in psoriatic plaques both iNOS and arginase are overexpressed,5 allowing low levels of NO to be produced locally. Furthermore, psoriasis affects vessels in the form of endothelial dysfunction, causing an accumulation of NOS inhibitors in the blood of patients with psoriasis,6 and also determining decreased free NO content in blood.7 Simultaneously, blood transports the locally produced proinflammatory cytokines that act on other systems, creating inflammation. NO is also produced physiologically by respiratory epithelium and endothelium.4 Inflammation can further increase the amount of NO by implementing iNOS expression. Thus, fractional exhaled NO (FeNO) has been accepted in the literature as an indirect marker of airway inflammation, and is currently used in the clinical monitoring and management of asthma inflammation levels.8 Owing to five studies that published inconsistent findings on the possible increased risk of patients with psoriasis having chronic obstructive pulmonary disease (COPD), the respiratory implications of psoriasis are not fully understood.2 9 10 11 12 Only one study has underlined a higher prevalence of asthma in people with psoriasis.4 The possibility of subclinical airway inflammation remains open and unevaluated. Thus, we examined this by comparing the FeNO levels of patients with psoriasis before and after treatment. In this observational study, we enrolled 59 patients with psoriasis who were admitted to our department in 2012–13. All patients had a Psoriasis Area Severity Index (PASI) score > 10, and were subdivided into two groups: moderate (10 < PASI < 20; n =42) and severe (PASI > 10; n =17). Diagnosis was based on a dermatological examination of the typical primary lesions. Exclusion criteria included nicotine dependence, atopy and other conditions that can change FeNO levels,4 while inclusion criteria included a Tiffeneau index > 80% and average forced expiratory flow during the mid (25–75%) portion of the forced vital capacity of > 65%, routinely measured with spirometry. Patients performed the FeNO test before and after treatments, and FeNO levels were detected by a high‐resolution chemiluminescence NO analyser at flow rates of 30, 50, 100 and 200 mL s−1. The result was the mean of three measurements acquired at each flow rate.4 Demographic characteristics were grouped with descriptive statistics and analysed by spss 21 (IBM, Armonk, NY, USA). All continuous data were expressed with the mean and SD. If normally distributed, the means were compared by Student's t‐test for independent samples and correlation between variables by linear regression with Pearson Index. Categorical variables were estimated by the χ2 test. A P‐value < 0·05 was considered significant. Patient data and descriptive statistics are shown in Tables 1 and 2, respectively. Patient characteristics BMI, body mass index; PASI, Psoriasis Area Severity Index. Patient characteristics BMI, body mass index; PASI, Psoriasis Area Severity Index. Statistical analysis results FeNO, fractional exhaled nitric oxide; PASI, Psoriasis Area Severity Index. Statistical analysis results FeNO, fractional exhaled nitric oxide; PASI, Psoriasis Area Severity Index. Before treatment, for all flows, patients had higher‐than‐normal FeNO levels compared with post‐treatment flows, when patients had normal FeNO levels. This difference was statistically significant and is shown in Figure 1(a). (a) Fractional exhaled nitric oxide (FeNO) at different flow rates in patients with psoriasis before and after treatment. (b) Correlation between FeNO at a flow rate of 30 mL s−1 and Psoriasis Area of Severity Index (PASI) score before treatment. (c) Correlation between FeNO at a flow rate of 50 mL s−1 and PASI score before treatment. (d) PASI severity groups (moderate and severe) compared at a FeNO flow rate of 30 mL s−1 before treatment. (e) PASI severity groups (moderate and severe) compared at a FeNO flow rate of 50 mL s−1 before treatment. (f) PASI severity groups (moderate and severe) compared at a FeNO flow rate of 100 mL s−1 before treatment. (g) PASI severity groups (moderate and severe) compared at a FeNO flow rate of 200 mL s−1 before treatment. There was positive correlation between PASI score and FeNO, especially for flow rates of 30 and 50 mL s−1 (Fig. 1b,c). A statistically significant difference was also seen between FeNO values for all flows and moderate and severe PASI scores, particularly at a flow of 50 mL s−1 (Fig. 1d–g). Furthermore, before and after treatment, FeNO scores were significantly different at all flow rates in both the moderate and severe PASI groups (Fig. 1a). In contrast to the literature, no sex or body mass index differences with regard to FeNO levels were detected in this study. Here, we have shown, for the first time, the detection of subclinical respiratory inflammation in patients with psoriasis by measuring FeNO. The mean FeNO values for all flows measured before treating patients with psoriasis were higher than normal, outlining a diffuse airway inflammation involving the entire respiratory tree. However, persistent inflammation may produce a noteworthy change of airway microstructure, decreasing dynamicity and functionality.13 Microstructure change may reflect a loss of function and a risk of developing respiratory diseases such as COPD or asthma. Five studies have analysed a possible increase of pneumopathies in patients with psoriasis, but with discordant results.2 Therefore, a demonstration of chronic subclinical inflammation could be useful in identifying the underlying biological mechanism contributing to the aetiology of chronically compromised respiratory function. The data presented here underlie the fact that if patients with psoriasis receive treatment, FeNO values for all flows normalize.14 This observation is in accordance with studies that have described a statistically significant decrease of proinflammatory cytokine levels in blood after biological and traditional systemic anti‐inflammatory therapies.15 Our study reveals that before treatment the FeNO levels of patients with psoriasis are higher than normal, so the presence of subclinical active airway inflammation could be a risk factor linked to the possibility of developing COPD.2 8 12 FeNO values were found to be correlated with overall PASI scores, as well as when patients were divided into moderate and severe PASI groups. This suggests that a dermatological tool evaluating the severity of psoriasis may serve as a rapid, inexpensive, noninvasive method of predicting airway inflammation. FeNO is a fast and sensitive marker with which to monitor the effectiveness of therapy.4 Post‐treatment FeNO levels in the severe PASI group did not match those seen in patients included in the moderate PASI group. Different first‐level PASI scores mean different starting levels of inflammation and, quantitatively, a different effect of therapy in reducing airway inflammation. PASI, which is correlated to FeNO, may also be a useful test in deciding the therapeutic strategy for psoriasis and in evaluating respiratory inflammation. Therapy could potentially be performed to decrease the risk of respiratory comorbidities. In conclusion, we detected subclinical respiratory inflammation, which does not currently require treatment and is unknown whether to be a true predictor of subsequent COPD or other lung disease. People with more severe psoriasis may have an increased risk of airway inflammation and therefore respiratory disease. Consequently, more effort has to be made in order to stratify the concomitant respiratory risk factors in patients with psoriasis. Future studies are required to clarify the cellular and cytokinetic background of airway inflammation to clarify it as being a psoriatic pathogenesis. Funding sources: none. Conflicts of interest: none declared.