Respiratory Function Changes as Early Signs of Amyotrophic Lateral Sclerosis.

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking. OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines. METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in 35 patients with unspecific neurological symptoms at the time of the visit and those were subsequently diagnosed with ALS 2 years after the initial visit ("pre-ALS"); we compared these patients with 29 patients with established ALS and with 28 control subjects. RESULTS: Spirometric parameters were not different between the three groups. However, MIP was significantly lower and P0.1 was significantly increased (with the ratio P0.1/MIP significantly higher) in both established and pre-ALS patients compared to controls, while both MIP and P0.1 were similar between established ALS and pre-ALS. CONCLUSIONS: Changes in MIP, P0.1, and P0.1/MIP ratio are highly suggestive of preclinical ALS when the spirometry and neurodiagnostic tests are still inconclusive. MIP and P0.1 are noninvasive measurements that can be easily assessed in an ambulatory setting. Future studies on larger cohorts are needed to validate the use of these parameters in the preclinical diagnosis of ALS as well as in other neuromuscular diseases.

Endobronchial Ultrasound for Benign Tracheal Stenosis.

We reported the role of endobronchial ultrasound as complement to standard diagnostic exams to better define the benign tracheal stenosis (i.e., thickness and tracheal cartilage integrity) and to plan the treatment with flexible instead of rigid bronchoscope. Under sedation and spontaneous ventilation, the flexible bronchoscope was inserted through the laryngeal mask airway that assured the ventilation. The stenosis was first resected with cold scissors and then dilated with balloon catheter. This strategy was successfully applied in five consecutive patients. Inclusion criteria for the procedure were stenosis < 1 cm in length, without tracheomalacia and with integrity of airway cartilage.

Effects of sex hormones on bronchial reactivity during the menstrual cycle.

BACKGROUND: Many asthmatic women complain of symptom exacerbations in particular periods, i.e. during pregnancy and menstrual cycles (perimenstrual asthma: PMA)". The goal of this study was to study the effect of the luteal and follicular phases of the menstrual cycle on bronchial reactivity (BR) in a group of asthmatic women. METHODS: For this purpose, 36 pre-menopausal women were enrolled and underwent testing for resting pulmonary function, measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured plasma hormone levels and levels of cyclic adenosine monophosphate (cAMP; a mediator of bronchial smooth muscle contraction) and testosterone in induced sputum samples. RESULTS: Our study showed that about 30% of the asthmatic women had decreased PC20FEV1.0 in the follicular phase of menstrual cycle with a significant correlation between PC20FEV1.0 and serum testosterone levels. Moreover, marked increases in sputum testosterone levels (mean=2.6-fold increase) together with significant increases in sputum cAMP concentrations (mean=3.6-fold increases) were observed during the luteal phase of asthmatic patients, suggesting that testosterone contributes to the pathophysiology of PMA. We excluded the possibility that testosterone directly inhibits phosphodiesterase (PDE) activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity. CONCLUSIONS: In conclusion, our data show that PC20FEV1.0 was decreased in the follicular phase of the menstrual cycle in about 30% of women and was associated with lower cAMP levels in sputum samples, which may contribute to bronchoconstriction. Our results also suggest a link between PMA and testosterone levels. However, whether these findings are of clinical significance in terms of the management of asthma or asthma worsening during the menstrual cycle needs further investigation.

Diagnosis of amyotrophic lateral sclerosis by respiratory function test.

The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, as the disease progresses, it is increasingly enriched by a rich set of symptoms and positive respiratory tests until respiratory failure occurs, which represents the main cause of death in ALS. Hereby we analyze the main pulmonary function tests (PFT) in the various stages of the disease, up to the recent evidence for the possibility of an early diagnosis.

Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features.

OBJECTIVE: To assess internal organ involvement in early SSc at presentation. METHODS: One hundred and fifteen patients admitted to a tertiary centre because of RP, who did not present any routinely detectable scleroderma-related internal organ involvement, were investigated for ANA and videocapillaroscopy, and underwent history and physical examination to detect symptoms/signs suggestive of SSc. Patients were then subdivided into three groups: (i) early SSc, constituted by patients without clinical manifestations other than RP, but with scleroderma marker autoantibodies and/or typical capillaroscopic abnormalities; (ii) probable SSc, constituted by patients with the same autoantibody and/or capillaroscopic status as early SSc patients, but with any of the following manifestations: digital ulcers/scars, puffy fingers, arthritis, telangiectasia, dysphagia/heartburn, shortness of breath; (iii) UCTD, constituted by patients with a specific (i.e. disease antibody marker) ANA and capillaroscopic findings plus any disease manifestation. All patients were investigated by lung functional study and B-mode echo-Doppler-cardiography. Patients who consented underwent oesophageal manometry. RESULTS: An inverted mitral E : A ratio (i.e. early scleroderma cardiac involvement) and/or a diffusing lung capacity for CO <80% of the predictive value (i.e. early lung involvement) and/or basal low oesophageal sphincter pressure <15 mmHg (i.e. early oesophageal involvement) were detected in 37/51 probable SSc patients (72%), 8/19 early SSc patients (42%) and 12/45 UCTD patients (27%). CONCLUSION: A scleroderma-related internal organ involvement was detected in patients from each group and, more importantly, was pre-clinical in a number of cases.

Ultrasound-Guided Anterior Mediastinotomy: A Feasible Tool for Critical Lymphoma Patients.

A significant part of all neoplasms growing in anterior mediastinum are lymphomas (25%). Achieving a correct diagnosis and a clear definition of a lymphoma's subtype is crucial for beginning chemotherapy as soon as possible. However, most patients present a large mediastinal mass that compresses vessels and airway, with serious cardiorespiratory repercussions. Therefore, having multiple tools available to biopsy the lesion without worsening morbidity becomes fundamental. Patients enrolled in this study were unfit for a surgical biopsy in general anesthesia and the need to begin chemotherapy as fast as possible prompted us to avoid percutaneous fine needle aspiration to prevent diagnostic failures. Our observational study included 13 consecutive patients with radiological findings of anterior mediastinal mass. Ultrasonography was performed directly in the theatre to mark the lesion and to localize vessels and vascularized neoplastic tissue. Open biopsy was carried out in spontaneous breathing with a laryngeal mask and with short-acting medications for a rapid anesthesia, performing an anterior mediastinotomy. The mean operative time was 33.4 ± 6.2 min and spontaneous respiration was maintained throughout the procedure. No complications were reported. All patients were discharged in the first or second postoperative day after a chest X-ray (1.38 ± 0.5 days). The diagnostic yield of this approach was 100%. With the addition of ultrasonography right before the procedure and with spontaneous breathing, anterior mediastinotomy still represents a useful tool in critical patients that could hardly tolerate a general anesthesia. The diagnostic yield is high, and the low postoperative morbidity allows a rapid onset of chemotherapy.

Air pollution and carotid arterial stiffness in children.

BACKGROUND AND PURPOSE: Many studies unequivocally indicate that air pollution is directly linked to the adverse cardiovascular outcomes in the general population. No data are currently available on cardiovascular effects of exposure to trafficked roads in healthy children. Distance of the residence to a major road has been shown to be a useful proxy for long-term traffic exposure and seem to be more consistently associated with atherosclerosis than particulate matter 2.5. The aim of this study was to investigate a possible association between the distance to a major road and carotid arterial subclinical markers of atherosclerosis in a group of children in Italy. METHODS: The participants consisted of 52 healthy children living in a small town of the Amalphitan Coast with only one highly trafficked road. All children underwent an ultrasound carotid arterial examination. RESULTS: A statistically significant difference was found in carotid arterial stiffness between children living closer to the main street and other children, both those living between 330 and 730 metres from the main street and those living more than 750 metres from the main street. No significant differences were detectable in carotid arterial thickness and arterial blood pressure among the three groups of children. CONCLUSION: This study provides evidence in support of an association of exposure to air pollution with early atherosclerotic markers in healthy children. Impaired vascular health in childhood and adolescence gives further substance to the hypothesis that traffic exhausts are relevant to cardiovascular diseases even early in life.

Sexual intercourse and respiratory failure.

Sexual activity is an important component of quality of life in patients suffering from chronic illnesses. To our knowledge, the effects of sexual activity on gas exchange in patients with respiratory failure have not been yet studied. To such an extent, we evaluated the oxygen saturation (SaO2), by a pulse oxymeter, during three different sexual performances in a 63-yr-old patient affected by chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy (LTOT). The sexual performances were divided in four periods: basal, sex, 10 min after sex and relax. In each performance during sex, we observed a significant increase of either heart rate (HR) or SaO2, with the highest value of the latter achieved within the 10 min of the post-sex period. SaO2 returned to basal value (pre-sex) by the end of the relax period. We conclude that the observed improvement of SaO2 during sexual activity might be due to a better ventilation/perfusion ratio (V/Q) obtained for either an increase of ventilation (hyperventilation) and perfusion (tachycardia), without significant muscle expenditure.

Ultrasound Fissure Observation: Assessment of Lung by Pleural-Hub Affiliates.

BACKGROUND: Lung ultrasound examination is becoming an even more important part of pulmonologists' clinical routine. As indicated in the literature, the coordinates of any findings on lung parenchyma are based on surface landmarks or conventional quadrants. In our experience we have noticed that lung fissures are clearly detectable as interruptions of the pleural line, but this has never been investigated previously. The aim of this study was to evaluate whether lung fissures are detectable under normal conditions in routine clinical practice. METHODS: Ten operators were enrolled from Pleural-Hub, a scientific discussion group. After compiling a prestudy survey to investigate whether they had observed fissures previously, they were asked to note if the following fissures were detectable: posterior right (PR) and left (PL), lateral right (LR) and left (LL), anterior right (AR), and anterolateral left (AL). Enrollment was competitive, aiming to reach 100 case subjects. RESULTS: We found that general fissure detection was 61.3%, in particular: PR, 59%; LR, 75%; AR, 69%; PL, 45%; LL, 64%; AL, 56%. Single operators yielded different detection rates ranging from 90% to 25%, showing strong operator dependency. Before being made aware of general results operators indicated operator's skill and rib shadow artifacts as the principal factors affecting fissure detection. CONCLUSIONS: Lung fissures may be detected with ultrasound once adequate training is provided. This may allow the clinician a more precise anatomical delineation of pathology identified by lung ultrasound.

In the era of ultrasound technology, could conventional trans-bronchial needle aspiration still play a role in lung cancer mediastinal staging?

BACKGROUND: To evaluate the feasibility of a combined strategy including conventional-trans-bronchial needle aspiration biopsy (C-TBNA) and endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) for sampling mediastinal adenopathies in patients with lung cancer in order to determinate whether in the era of ultrasound technology C-TBNA could still play a role in mediastinal staging. METHODS: It was a retrospective multicenter study including all consecutive patients with lung cancer and radiological mediastinal adenopathies undergoing TBNA for mediastinal staging (January 2014 - July 2016). C-TBNA was performed as first diagnostic procedure. All negative C-TBNA results were corroborated by EBUS-TBNA, and, if EBUS-TBNA was negative, by mediastinoscopy or surgery. The diagnostic yield of C-TBNA were then calculated. RESULTS: A total of 175 patients were included in the study for a total of 197 mediastinal adenopathies sampled. C-TBNA was positive in 125 cases and negative in 72 cases who underwent EBUS-TBNA. It was positive in 58 cases and negative in 14 patients. After surgical exploration (n=12) and mediastinoscopy (n=2), 11 patients did not present metastases (true negative) while 3 presented mediastinal involvement (false negative). Thus, C-TBNA had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 67.2%, 100%, 100%, 15.3% and 69.0%, respectively. The sensitivity increased for sampling paratracheal versus subcarinal stations (80% versus 49%; P<0.001); and large adenopathies (≥15 mm) versus small adenopathies (<15 mm) (83% versus 43%; P<0.001). In all re-staging patients (n=4), Conventional-TBNA results were false negative. CONCLUSIONS: The combined use of C-TBNA and EBUS-TBNA as the most cost-effective strategy in the setting of mediastinal staging. C-TBNA performed before EBUS-TBNA is indicated for sampling large mediastinal adenopathies near to carina while EBUS-TBNA remains the first choice for puncturing small adenopathies far from carina and for re-staging after induction therapy.

Three-dimensional virtual bronchoscopy using a tablet computer to guide real-time transbronchial needle aspiration.

Objectives: We proposed a new virtual bronchoscopy tool to improve the accuracy of traditional transbronchial needle aspiration for mediastinal staging. Methods: Chest-computed tomographic images (1 mm thickness) were reconstructed with Osirix software to produce a virtual bronchoscopic simulation. The target adenopathy was identified by measuring its distance from the carina on multiplanar reconstruction images. The static images were uploaded in iMovie Software, which produced a virtual bronchoscopic movie from the images; the movie was then transferred to a tablet computer to provide real-time guidance during a biopsy. To test the validity of our tool, we divided all consecutive patients undergoing transbronchial needle aspiration retrospectively in two groups based on whether the biopsy was guided by virtual bronchoscopy (virtual bronchoscopy group) or not (traditional group). The intergroup diagnostic yields were statistically compared. Results: Our analysis included 53 patients in the traditional and 53 in the virtual bronchoscopy group. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the traditional group were 66.6%, 100%, 100%, 10.53% and 67.92%, respectively, and for the virtual bronchoscopy group were 84.31%, 100%, 100%, 20% and 84.91%, respectively. The sensitivity ( P = 0.011) and diagnostic accuracy ( P = 0.011) of sampling the paratracheal station were better for the virtual bronchoscopy group than for the traditional group; no significant differences were found for the subcarinal lymph node. Conclusions: Our tool is simple, economic and available in all centres. It guided in real time the needle insertion, thereby improving the accuracy of traditional transbronchial needle aspiration, especially when target lesions are located in a difficult site like the paratracheal station.

Bronchoscopic lung volume reduction with endobronchial valves for heterogeneous emphysema: long-term results.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with implant of one-way endobronchial valves (EBV) is a feasible treatment for management of heterogeneous emphysema (HE) with clinical benefits in the early follow-up. We aimed to evaluate the long-terms results and safety of this procedure in a consecutive series of patients with HE. METHODS: It was a retrospective single center study including all consecutive patients with HE undergoing EBV treatment and completing at least 5 years of long-term follow-up. Patients were splitted into Collapse and No-Collapse Group if a lobar collapse or not were obtained after valves implant. The difference of functional data and quality of life (QoL) before and after the procedure (measured at 3, 6, 9, 12 months from the valve implantation, and then annually up to a maximum of 5 years) were statistically evaluated to show the long-term benefits of the procedure (primary endpoint). Yet, morbidity, mortality and survival rates were also recorded to show the safe of the treatment (secondary endpoint). RESULTS: Thirty-three patients were included in the study. Of these, three patients underwent a bilateral treatment. Collapse Group patients (n=27) presented a significant improvement in FEV1% (+17%; P=0.001); in FVC% (+18%; P=0.002); in RV% (-39%; P=0.003); in 6MWT (P=0.001) and in SGRQ (P=0.001) in the early 12 months of follow-up and no significant decline was seen later. Conversely, No-Collapse Group (n=9) did not have significant benefits. No major complications and death related to the procedure were observed. The 1-,2-,3-,4- and 5-year survival rates were 100%, 90%, 78%, 71% and 71%, respectively. Collapse Group had a better survival than No-Collapse Group (45 vs. 24 months; P=0.001). CONCLUSIONS: Our study confirmed that the lobar collapse is the key success of EBV treatment and the early improvements of respiratory function could be maintained up to five years from the valves implant.

Recumbent deoxygenation in mild/moderate liver cirrhosis: the "clinodeoxia". The ortho-clino paradigm.

BACKGROUND: While the effects of postural change on arterial oxygenation have been well documented in normal subjects, and attributed to the relationship of closing volume (CV) to the tidal volume, in liver cirrhosis such postural changes have been evaluated mainly in a rare, peculiar clinical end-stage condition which is characterized by increased dyspnea shifting from supine to upright position ("platypnea"). The latter is associated with worsening of PaO2 ("orthodeoxia"). We evaluated the effects of postural changes on arterial oxygenation in patients affected by mild/moderate liver cirrhosis. METHODS: We performed pulmonary function tests and arterial blood gas evaluation in sitting and supine positions in 22 patients with mild/moderate liver cirrhosis, biopsy-proved, and 22 matched non-smokers control subjects. RESULTS: Recumbency elicited a decrease of PaO2 (Δ(sup-sit)PaO2) in 19 out of 22 controls and in all but one cirrhotics. The magnitude of this postural change was significantly (p = 0.04) greater in cirrhotics (9.6 ± 5.3%) compared to controls (6.7 ± 3.7%). In the subset of cirrhotics younger than 60 yrs and with PaO2 greater than 80 mmHg in sitting position, the Δ(sup-sit)PaO2 in recumbency further increased to 12 ± 5.8%, significantly (p = 0.014) greater than in same subgroup of controls (7.1 ± 3.8%). CONCLUSIONS: In mild/moderate liver cirrhosis the postural variations in PaO2 follow the normal trends, but are of greater magnitude probably as a consequence of hypoventilated units of lung for postural and disease-linked tidal airway closure, resulting in more pronounced recumbent hypoxemia ("clinodeoxia").

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

Respiratory diseases in Italy already now represent an emergency (they are the 3(rd) ranking cause of death in the world, and the 2(nd) if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document "Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)" of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document - produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise -after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,'case-finding'approach; assessment of the individual's level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the "systemic", consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents.

Early systemic sclerosis: analysis of the disease course in patients with marker autoantibody and/or capillaroscopic positivity.

OBJECTIVE: To investigate whether patients affected by 1 of the 3 subsets of early systemic sclerosis (SSc; scleroderma), i.e., subset I, Raynaud's phenomenon with SSc marker autoantibodies and typical capillaroscopic findings; subset II, autoantibody positive only; and subset III, capillaroscopy positive only and not satisfying the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for SSc at admission, differ from each other in the time to satisfy the criteria. METHODS: Early SSc patients subdivided into the 3 subsets indicated above consecutively admitted to a rheumatology/angiology center were monitored for 12-102 months (median 36 months). Patients were reevaluated twice yearly to assess whether and when each patient satisfied the new ACR/EULAR classification criteria for SSc. Patients with undifferentiated connective tissue disease (UCTD) served as the comparator group. RESULTS: During followup, 11 (52.3%) of 21 subset I, 10 (66.6%) of 15 subset II, 0 of 24 subset III, and 0 of 44 UCTD patients satisfied the criteria (P = 0.0001). The difference was significant between early SSc and UCTD patients (P = 0.0001) and, within the group of early SSc patients, between each of the 2 autoantibody-positive subsets (subsets I and II) and the capillaroscopic-positive/autoantibody-negative subset (subset I versus III: P = 0.0001; subset II versus III: P = 0.0009). There was no difference between the 2 autoantibody-positive subsets (P = 0.454). In addition to marker autoantibody positivity, preclinical lung or heart involvement was associated with an increased risk to satisfy the criteria during followup. CONCLUSION: Our data demonstrated faster progression of SSc in autoantibody-positive patients, particularly in those with preclinical internal organ involvement at baseline, than in autoantibody-negative patients.

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers.

INTRODUCTION: Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear. METHODS: Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation. RESULTS: Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies. CONCLUSION: These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.

C-reactive protein and carotid intima-media thickness in children with sleep disordered breathing.

STUDY OBJECTIVES: Obesity is a risk factor for sleep disordered breathing (SDB) in children. Plasma levels of high-sensitivity C-reactive protein (Hs-CRP) are predictive of cardiovascular morbidity in adults, and CRP levels are associated with over-weight. Increased carotid intima-media thickness (IMT) is associated with several cardiovascular risk factors. We evaluated the effect of SDB on CRP levels and IMT in lean and obese children not selected for snoring. METHODS: 101 children (age 5-15 years) attending a weight clinic or scheduled for routine visit. IMT was measured with quantitative B-mode ultrasound scans. The apnea-hypopnea index (AHI) was measured overnight: AHI < 1 defined controls, AHI ≥ 1 to < 5 = mild SDB, and AHI ≥ 5 = obstructive sleep apnea (OSA). RESULTS: AHI was significantly associated with Hs-CRP concentration (r = 0.32, p = 0.002) in all 101 children irrespective of age and sex. Body mass index (BMI) was higher in OSA children than controls (25.5 ± 7.0 vs 22.1 ± 6.9, p = 0.05). Obese children had 3.3 times more probability of having OSA (HR 3.3, 95% CI 1.2-9.3, p = 0.02) than lean children. Hs-CRP values were significantly higher in children with OSA than in children without (p = 0.011), but not when BMI z-score was added as covariate. IMT was not associated with AHI or SDB. CONCLUSIONS: The results of this study suggest an association between OSA and Hs-CRP concentrations (mainly mediated by overweight and obesity), but not between OSA and subclinical atherosclerosis. There is scope for prevention in childhood before OSA syndrome causes the irreversible damage to arteries observed in adult patients.