Background: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID-exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro-inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective:We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA).Methods: A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA.Results: Three classes (subphenotypes) were distinguished within the NERD cohort.Class 1 subjects had mild-to-moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE 4 /logPGE 2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro-inflammatory LTE 4 in ISS and the highest logLTE 4 /logPGE 2 ratio. Class 3 subjects had mild-to-moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro-(LTE 4 , PGD 2 and 11-dehydro-TBX 2 ) was balanced by

A 22-year-old man was admitted to the Immunology Department because of rapidly progressive skin hardening. In the previous two years he was treated with methylprednisolone and azathioprine for autoimmune hepatitis. On admission the patient presented with massive hardening of the skin of the lower part of the face (causing severe microstomia), and skin of the neck, chest, abdomen, and upper limbs, lower limbs were involved to a lesser extent. The involved skin was hardened, shiny, and dry with exfoliating epidermis. Capillary refill was delayed. The patient was cachectic and reported difficulty with swallowing solid food. He also complained of hoarseness and a sore throat. His speech was slurred. A throat examination was impossible to perform due to microstomia. Family history was positive for liver and testicular cancer. The skin started to harden four months prior to admission, and since then the patient was thoroughly screened to exclude any neoplasm. Gastroscopy revealed inflammatory infiltrates in the stomach; colonoscopy was negative. Urological examination including testicular ultrasound was normal. Chest computed tomography revealed multiple ground glass opacities. Cultures from the material collected during bronchoscopy showed Pseudomonas aeruginosa. Antibiotics were started. Lung tests revealed reversible airway obstruction and mild pulmonary hypertension. He was then consulted by the cardiologist, who did not find signs of right ventricular overload or cardiac failure and suggested further observation. On admission the patient's vital signs were within normal range (heart rate 95 bpm, blood pressure 120/80 mmHg, haemoglobin oxygen saturation 96%) and did not change significantly during hospitalisation. He presented mild anaemia (haemoglobin 11.6 g/dL), elevated platelet count (402 × 10 3 /µL), monocytes (1.56 × 10 3 /µL), and eosinophils (0.89 × 10 3 /µL). Serum albumin level and cholinesterase activity were slightly decreased. International normalised ratio was 1.18. C-reactive protein and lactate dehydrogenase were elevated. Polyclonal hypergammaglobulinaemia was present. Electrocardiogram was impossible to obtain because of severe skin hardening causing multiple artefacts. Heart ultrasound showed traces of fluid in the pericardium. Left ventricular ejection fraction was ~65%. There was no thickening of the heart muscle or hypokinesis. Pulmonary artery systolic pressure was estimated around 40 mmHg using continuous Doppler wave method. Barium swallow examination of the oesophagus revealed dysmotility. Anti-nuclear antibodies were positive in immunofluorescence test (titre 1:320) with a speckled pattern, but specific identification was negative on immunoblot. Skin and muscle biopsy showed fibrosis of the skin and fascia with mild inflammation in the epimysium. The patient was diagnosed with diffuse systemic sclerosis and received two 250-mg pulses of methylprednisolone followed by 1 mg/kg body weight daily IV dose. Topical steroids were also applied. The patient initially reported improvement in skin t...