Lung Involvement in Undifferentiated Connective Tissue Diseases: A Rheumatology Perspective

Objectives: Studies pointing out the occurrence of Interstitial Lung Diseases (ILD) in Undifferentiated Connective Tissue Diseases (UCTD) have been so far derived from patients admitted to Respiratory Medicine Units. We undertook the present prospective study to investigate for the presence of lung involvement, patients admitted to a Rheumatology Unit and diagnosed as UCTD. Materials and Methods: Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography and lung function study according to previously reported methods. Moreover patients giving a further consent, underwent a high resolution computed tomography (HRCT) of lungs. Results: Six patients (7.4%) referred dyspnea grade II at history. Out of them 3 presented a DLCO ranging from 42 to 55% of the predicted value; and a HRCT documented ILD with a Non-Specific Interstitial Pneumonia (NSIP) pattern. The other 3 patients suffered from cardiac disease accounting for their symptoms. Out of the 75 asymptomatic patients, nobody presented relevant findings at physical examination, 26 resulted to have a DLCO <80% (<70% in 10 cases). Thirty out of these 75 patients accepted to undergo lung HRCT, that pointed out a NSIP-ILD in 3 cases. Conclusion: Six out of the 81 investigated were found to present a definite ILD which was symptomatic in half cases. A higher percentage of patients resulted to have a reduced DLCO, the meaning of which awaits to be investigated (preradiographicILD? Preechocardiographic pulmonary vascular disease? ). Antonella Riccardi1, Rosaria Irace1, Ilaria Di Stefano1, Michele Iudici1, Serena Fasano1, Marialuisa Bocchino2, Annalisa Capaccio2, Alessandro Sanduzzi2 and Gabriele Valentini1* 1Department of Internal and Experimental Medicine, Second University of Naples, Italy 2Department of Clinical Medicine and Surgery, University "Federico II", Italy Gabriele Valentini, et al. Journal of Respiratory Medicine and Lung Disease Remedy Publications LLC. 2017 | Volume 2 | Issue 1 | Article 1011 2 Second University of Naples from 1st January 2013 to 31st December 2015, were enrolled in the study, after giving a written informed consent. UCTD was diagnosed according to Mosca et al. [8] and Doria et al. [9]. Briefly, patients had to: a) presentsigns and symptoms suggestive of a CTD with out fulfilling the criteria of any definite CTD [8]; b) be anti-nuclear antibodies (ANA) positive; c) do not have either any CTD marker autoantibody (i.e. anti-dsDNA, anti-Sm, anti-ribosomal P protein, anti-Scl-70, anti centromere, anti-La/SSB, anti-Jo1, anti-Mi-2) or any manifestation distinctive of any major CTD (i.e. malar rash, subacute CLE, chronic CLE, skin sclerosis, heliotrope rash, Gottron’s plaques, erosive arthritis, alopecia) [9]; d) have a diseasedurationasassessed from the onset of the 1st symptom/ sign ≥ 3 years. Routine assessment According to standard clinical practice and to ensure a correct classification, each patient with a suspected UCTD underwent a detailed history and an accurate physical examination devoted to identify any of the previously referred featurespreventing enrolment in the study [8,9] as well the presence of symptoms/signs of ILD, namely dyspnea, graded according to NYHA and bibasilar crackles; routine laboratory investigations including blood cell count, urinalysis, blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), erythrosedimentation rate (ESR), serum protein electrophoresis, serum C3 and C4 concentration; nailfold videocapillaroscopy (NVC), antinuclear antibody (ANA) screening and profiling, B-mode echocardiography and lung function. Autoantibody profile assessment Autoantibodies were investigated in sera collected at the first visit, stored at −20°C and heated at 56°C for 30 min before testing. ANA and ACA were determined by IIF on HEp-2 cells (Astra srl, Pavone Canavese, Italy), using fluorescent anti-human gamma globulin as conjugate, using a 1: 160 serum dilution as cut-off value. Anti-Scl-70, anti-SSA, anti-SSB, anti-Sm, anti-Jo1 and anti-U1RNP were identified with commercially available ELISA kits (Chematil srl, Angri, Italy), using 25 U/ml as cut-off value. Anti-RNA polymerase III, antifibrillarin and anti-Pm-Scl were investigated by EliA Varelisa Phadia test (Germany) using 150 U/ml as cut-off value. Anti-Th/To were investigated by western blotting technique (Arnikasrl, Milan, Italy). Anti-DNAds antibodies were identified by IIF on Crithidialuciliae at a serum dilution of 1: 10 (Astra srl) [10]. Nailfold videocapillaroscopy assessment Patients were investigated for typical microvascular alterations (megacapillaries and/or avascular areas) by nailfold Videocapillaroscopy (NCV). NCV was carried out while the patients were seated with their hands positioned at heart level, and at a room temperature of 22–25°C. A drop of immersion oil was applied to the nailfold to increase the translucency of the keratin layer. All the fingers were examined by the same physician (R.I.) who is experienced in NCV using a video capillaroscope (Video cap 25-DS Medica; Freiburg, Germany) with optical probes of ×200. The degree of capillary enlargement on a scale of 0–3 and capillary loss (Grades A–D) were considered. Megacapillaries (capillary enlargement ≥2) and/or avascular areas (capillary loss Grade ≥C) were considered a scleroderma pattern [11]. Assessment of internal organ involvement All patients underwent B-mode echocardiography and lung function study. Echocardiographic examination was performed as described elsewhere [12]. The detection of either a diffusing lung capacity for CO (DLCO) or a forced vital capacity (FVC) <80% of the respective predicted values in the absence of smoking, obstructive lung disease and/or cardiac involvement was considered indicative of possible ILD [13,14]. Moreover, patientsgiving a further consent underwent a high resolution computed tomography of lungs (Lung HR-CAT). Chest HRCT images were obtained with 1-mm collimation and 10-mm intervals at maximal endinspiratory phase with the patient in a supine position using a high spatial frequency algorithm. If needed, prone scans were added to distinguish gravity-related changes from structural abnormalities. According to Fischer et al. [15], the presence of a non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organising pneumonia (OP), lymphoid interstitial pneumonia (LIP) wereconsidered consistent with a diagnosis of ILD. Statistical analysis We used the SPSS for Windows software (version 16.0) for statistical analysis. Categorical data were analyzed by contingency table (Chi square). A p value <0.05 was considered significant. The study was approved by the ethics committee of the Second University of Naples.