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Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities. A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement. We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

Aims To investigate changes in retinal vessel diameter during acute hyperglycemia in patients with type 1 diabetes. Methods We conducted a study on 11 subjects with type 1 diabetes. Euglycemia was maintained for 3 h followed by induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two fundus photos were captured during euglycemia and five fundus photos, blood glucose and blood pressure were taken every 30 min for 2.5 h post-prandial. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were measured over the study visit and examined using generalized linear mixed models. Results In a multivariate mixed model, mean CRAE and CRVE were reduced at 90 min post-prandial in both zones B and C. In repeated measures analysis, arterioles exhibited a significant association with change in vessel caliber per change in blood glucose. Inconsistent effects of blood pressure on vessel diameter were also measured. Conclusions We document a change in retinal vessel diameter during acute hyperglycemia in persons with type 1 diabetes. Larger controlled studies are required to further investigate this phenomenon and to more accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

Besides environmental triggers, a family history of asthma is a strong risk factor for the development of asthma in offspring. The pooled data from 13,963 interviews of randomly selected, 20 to 48 yr-old participants from the 30 centers of the European Community Respiratory Health Survey (ECRHS) were analyzed with conventional logistic regression and a Class A regressive model adapted for the segregation of various transmission modes in families. The asthma prevalence in the interviewed index generation was 6.9% (95% confidence interval [CI]: 6.5 to 7.3), and in the parent generation was 6.1% (5.8 to 6.4). As with asthma prevalence, the risk of a subject having asthma if a parent had asthma also had a large geographic variation across the survey centers. The mean risk if a father had asthma was 2.9 (2.4 to 3.5), and If the mother had asthma was 3.2 (2.6 to 3.9). The risk increased to 7.0 (3.9 to 12.7) if both parents were affected. For developing extrinsic asthma, extrinsic asthma in any parent was a greater risk factor (4.9 [3.9 to 6.0]) than intrinsic asthma of the parent (1.5 [0.8 to 2.6]), and the risk for women was slightly higher than that for men (4.3 [3.3 to 5.5] versus 3.6 [2.6 to 5.0]). Applying different segregation models, only a model for a two-allele gene with a codominant inheritance could not be rejected, assuming a major gene with a population frequency of 24.2%. Further results make a multilocus/threshold model likely. In conclusion, a history of asthma in parents is a strong risk factor for asthma in the offspring. Under the assumptions of the applied segregation analysis, at least one major gene exists which could be a gene involved also in allergy. However, asthma is not fully described by a single-gene model. The risk for asthma varies within the European countries, and should be seen in the context of a complex genetic and environmental pathophysiology.

Chronic cough is more frequent and severe in women than in men. Women often have decreased iron stores, because of menses and pregnancies. We investigated if iron deficiency has a role in chronic cough by increasing airway sensitivity to inhaled irritants.Twenty-two non-smoking women with chronic unexplained cough and iron deficiency (serum ferritin below 15 ng/ml) were examined in baseline, after 2 months empiric treatment with anti H1-histaminic drug and proton pump inhibitor, and after iron supplementation (330-660 mg iron sulphate tablets daily) for 2 months. Outcome measures were cough visual analogue scale (VAS), and histamine thresholds of the larynx (PC25MIF50, concentration causing 25% in MIF50), bronchi (PC20FEV1) and cough (PC5cough).Mean serum ferritin was 9.3 ng/ml (95% CI 7.7-10.9), 13 patients had mild anaemia. All the patients had laryngeal and cough hyperresponsiveness,12 had also bronchial hyperresponsiveness. Empiric treatment produced no significant effect, whereas iron supplementation improved cough VAS from 4.03 (3.6-4.47) to 2.6 (1.9-3.27), p0.0001, PC20FEV1 from 10.04 mg/ml (5.37-18.77) to 22.2 (11.7-41.8), p0.001, PC25MIF50 from 3.09 mg/ml (1.9-4.9) to 11.9 (7.3-19.4), p0.001 and PC5cough from 2.1 mg/ml (1.2-3.6) to 8.8 (5.2-15.1), p0.001.In women with unexplained chronic cough unresponsive to targeted treatment, airway and cough hyperresponsiveness may be sustained by iron deficiency. Healthy women with chronic cough should be checked for iron deficiency as iron repletion may resolve such disturbing symptom.

The role of mastication on digestion efficiency remains to be demonstrated. This study investigates whether masticatory function influences gastric emptying rate. Twelve normal volunteers were studied on two occasions after ingestion of the same test meal containing ham cubes, crackers, and egg (mixed with 13C-octanoic acid), chewed, in random order, either with 50 masticatory cycles or with 25 cycles, swallowing ham cubes whole. Lag phase (Tlag) and gastric half-emptying time (T½) were measured by means of the 13C-octanoic acid breath test. Trituration performance was assessed by the sieve test, and was expressed as the percentage of ham particles ≤ 1 mm after 50 masticatory cycles. Tlag and T½ were significantly shorter when the meal was chewed with 50 cycles than with 25 cycles (Tlag 25.9 ± 3.8 vs. 36.4 ± 4.1 min, p = 0.017; T½ 49.1 ± 5.7 vs. 62.5 ± 6 min, p = 0.009). Trituration performance was inversely related to both Tlag (r = 0.621, p = 0.031) and T½ (r = 0.699, p = 0.012). Comminution of food influences significantly gastric emptying rates.

Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non-autoimmune type 1 diabetes. The etiology involves a single gene mutation of the wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy, and sensory-neural deafness. Symptoms are initially absent and signs within the posterior segment of the eye are usually the earliest indicator of WS.These cases characterize unusual and poorly described findings of pigmentary maculopathy in WS and illustrate the importance of collaboration between diabetes and eye care providers; especially in cases of non-autoimmune type 1 diabetes exhibiting atypical human leukocyte-associated antigen haplotypes.

Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane.The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2) ) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen.At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.85, P0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.52, P=0.001).The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma.

Upper airway edema might contribute to pharyngeal collapsibility and account for the high prevalence of obstructive sleep apnea (OSA) in patients with heart disease. The aim of this study was to evaluate if intensive unloading with diuretics improves sleep-disordered breathing and increases pharyngeal caliber in patients with severe OSA and diastolic heart failure.Fifteen patients with severe OSA, hypertension, and diastolic heart failure were hospitalized to receive IV furosemide, 20 mg, and spironolactone, 100 mg, bid for 3 days. Polysomnography was performed for assessment of apnea-hypopnea index (AHI), acoustic pharyngometry was performed for assessment of the oropharyngeal junction (OPJ) area, and forced midinspiratory flow (FIF(50)), forced midexpiratory flow (FEF(50))/FIF(50) percentage, and exhaled nitric oxide (FeNO) were measured before and after diuretic treatment.Diuretic treatment produced a significant decrease in body weight, BP, and AHI (from 74.89 +/- 6.95 to 57.17 +/- 5.40/h, p0.001), associated with an improvement in OPJ area (from 1.33 +/- 0.10 to 1.78 +/- 0.16 cm(2), p = 0.007), FIF(50) (from 3.16 +/- 0.4 to 3.94 +/- 0.4 L/s, p = 0.006), and FEF(50)/FIF(50) percentage (from 117.9 +/- 11.8 to 93.15 +/- 10.1%, p = 0.002). Weight loss was significantly related to the decrease of AHI (R = 0.602; p = 0.018), to the increase of FIF(50) (R = 0.68; p = 0.005), and to the decrease of FEF(50)/FIF(50) (R = 0.635; p = 0.011).These findings suggest that pharyngeal edema contributes to sleep-disordered breathing in obese patients with severe OSA, hypertension, and diastolic heart failure. Upper airway edema may contribute to the frequent occurrence of OSA in patients with heart disease.

At present, allogeneic hematopoetic stem cell transplantation (AST) is the only potentially curative treatment for multiple myeloma. Its action is most likely due to an allogeneic graft-versus-myeloma effect. Unfortunately AST carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and to the graft versus host disease (GVHD), which may be life threatening.’ Pulmonary complications after AST are common2 and different in nature, ranging from opportunistic infections, such as invasive pulmonary aspergillosis, vascular abnormalities, such as pulmonary veno-occlusive disease and diffuse alveolar hemorrhage, and immune-mediated pulmonary processes, such as idiopathic pneumonia syndrome and bronchiolitis obliterans. The last is a nonspecific inflammatory injury of the small airways that was recognized in early 1980s, particularly among patients with acute and chronic GVHD and in those with respiratory infections. Non-myeloablative AST (NST) has the advantage of using low dose total body irradiation, less chemotherapy and more specific immune-modulation. For these reasons it is feasible in elderly patients with almost no upper age limit, in patients heavily pre-treated, and in those with organ dysfunction or other comor

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1–November 30, 1999, and 500 consecutive patients with asthma, aged 18–55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros () for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to 720, 1,046, 1,535 and 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative. This study was supported by a grant from Merck & Co., Inc., Whitehouse Station, NJ, USA.

The role of mastication on digestion efficiency remains to be demonstrated. This study investigates whether masticatory function influences gastric emptying rate. Twelve normal volunteers were studied on two occasions after ingestion of the same test meal containing ham cubes, crackers, and egg (mixed with 13C-octanoic acid), chewed, in random order, either with 50 masticatory cycles or with 25 cycles, swallowing ham cubes whole. Lag phase (Tlag) and gastric half-emptying time (T1/2) were measured by means of the 13C-octanoic acid breath test. Trituration performance was assessed by the sieve test, and was expressed as the percentage of ham particlesor = 1 mm after 50 masticatory cycles. Tlag and T1/2 were significantly shorter when the meal was chewed with 50 cycles than with 25 cycles (Tlag 25.9+/-3.8 vs. 36.4+/-4.1 min, p=0.017; T1/2 49.1+/-5.7 vs. 62.5+/-6 min, p=0.009). Trituration performance was inversely related to both Tlag (r=0.621, p=0.031) and T1/2 (r=0.699, p=0.012). Comminution of food influences significantly gastric emptying rates.

Respiratory disturbances during sleep are considered risk factors for arterial hypertension and cardiovascular diseases. Edentulism, by decreasing retro-pharyngeal space, may favor upper airway occlusion during sleep. Aim of the study is to evaluate whether edentulism is associated with greater prevalence of sleep disturbances, arterial hypertension and other cardiovascular diseases.Eighty edentulous subjects with dentures (removed during sleep) and 57 subjects with natural teeth, matched for age, underwent assessment of oral conditions and recording of questionnaires on diseases and respiratory sleep disturbances.Edentulous subjects had a significantly higher prevalence of arterial hypertension and cardiovascular diseases, than subjects with natural teeth.In edentulous subjects, removing dentures during sleep may favor respiratory disorders, and increase the risk for hypertension and cardiovascular disease.

Aim of the paper is to study whether edentulism, by causing a decrease in size and tone of pharyngeal musculature, may affect spirometric measurements.Spirometry was recorded with and without dentures in 58 edentulous subjects, 36 asymptomatic normal subjects (N) and 22 patients with chronic obstructive pulmonary disease (COPD). In 10 subjects retropharyngeal space with and without dentures was assessed by cephalometry.In the N group, removing dentures produced a significant decrease in lung volumes and airflow rates, while in COPD patients it was ineffective. In both groups, retropharyngeal space was significantly decreased by removing dentures.Edentulism, by decreasing extrathoracic airway caliber, influences significantly spirometric measurements in normal subjects but not in those with COPD.

Patients with asthma-like symptoms may not have asthma but obstruction of the extrathoracic airway (EA). To evaluate if dysfunction of the EA causes asthma-like symptoms, we assessed bronchial and EA responsiveness to inhaled histamine in 441 patients who presented with at least one of three key symptoms--cough, wheeze, dyspnoea--but had neither documented asthma nor bronchial obstruction. The histamine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) and a 25% fall in maximal mid-inspiratory flow (PC25MIF50) were used as respective thresholds of bronchial and EA responsiveness. Values 8 mg/mL or less indicated bronchial (B-HR) or EA hyper-responsiveness (EA-HR). The influence of concurrent upper respiratory tract diseases, such as post-nasal drip (PND), pharyngitis, laryngitis and sinusitis, was also assessed. We found four response patterns to the histamine challenge: EA-HR in 26.5% of the patients, B-HR in 11.1%, combined EA-HR and B-HR in 40.6%, and no-HR in 21.8%. Cough was reported by 79% of the patients, wheeze by 53%, and dyspnoea by 40%. Patients with cough as the sole presenting symptom (34.2%), as compared with those with wheeze and/or dyspnoea (20%), had significantly greater probability of having EA-HR (OR 5.35, 95% CI 3.25-8.82) and lower probability of having B-HR (OR 0.45, CI 0.28-0.70); patients with cough plus wheeze and/or dyspnoea (45.8%) had significantly greater probability of having both EA-HR and B-HR than either those with cough alone (OR 2.48, CI 1.49-4.13), or those with wheeze and/or dyspnoea but not cough (OR 1.74, CI 1.36-2.22). EA-HR alone or combined with B-HR was strongly associated with EA diseases, particularly pharyngitis and PND. Cough was significantly associated with PND, either when it was the sole symptom (OR 2.16, CI 1.14-4.09) or when it was combined with wheeze and/or dyspnoea (OR 3.53, CI 1.97-6.33). Our results suggest that extrathoracic airway dysfunction may account for asthma-like symptoms, particularly chronic cough. This abnormality seems to be sustained by chronic diseases of the upper respiratory tract.

Asthma associated with sinusitis is supposed to be sustained by bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors.The study was designed to evaluate the relationship between EA responsiveness and bronchial responsiveness in sinusitis.We performed histamine inhalation challenge in 106 patients with chronic sinusitis, during disease exacerbation and after treatment with antimicrobials and nasal flunisolide (100 micrograms daily) for 2 weeks. Forced expiratory volume in 1 second (FEV1) and maximal mid-inspiratory flow (MIF50) were the respective indexes of bronchial and EA narrowing; the histamine concentrations causing a 20% fall in FEV1 (PC20) and 25% drop in MIF50 (PC25MIF50) were used as thresholds of bronchial and EA responsiveness. Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR).During sinusitis exacerbation 76 patients had EA-HR, which in 46 was associated with B-HR. The values of PC20 were closely related with those of PC25MIF50 (p0.001). EA-HR and B-HR were strongly associated with pharyngitis. After treatment, mean PC25MIF50 and PC20 were significantly increased (p0.001). The improvement of PC25MIF50 was closely related to that of PC20 (p0.001) and to the decrease in neutrophils in nasal lavage (p0.05). EA-HR reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in 12.Our findings suggest that in sinusitis, B-HR may be sustained by constrictive reflexes originating in pharyngeal receptors, made hypersensitive by seeding of the inflammatory process.

Among the causes of anterior knee pain, impingement of portions of the infrapatellar fat pad between the femoropatellar and femorotibial articular surfaces plays an important role. This disease, first described by Hoffa in 1904, has always been fairly obscure. This review of 63 cases delineates the clinical features, distinguishing two phases, acute and chronic, and analyzing the pathologic changes in the fat pad and the other joint structures involved. Treatment of both the chronic and acute phases is described, emphasizing the importance of arthroscopy in the chronic phase. The arthroscopic techniques are thoroughly described and commented on. Analysis of the results confirms the validity of arthroscopic surgery in the treatment of this disease.

The glomus tumor, characterized by the classic trio of tumefaction, acute pain on palpation, and sensitivity to cold, is localized most commonly in the hand and quite rarely in the knee. It occurs most frequently in subjects between the ages of 20 and 40, and its cause is unknown. Masson divided glomus tumors into 4 main types: angiomatous, stromal, nervous, and myxoid, according to the histo-pathological features present. The authors believe that the histological appearance may be affected by the functional phase of the tumor at the moment of surgery: with sphincters closed, meaning very little dilatation of the venous collection areas, or with sphincters open, meaning considerable dilatation of the venous collection areas due to increased hematic flow.

The effect of acute oral administration of 2 g vitamin C on bronchial responsiveness to inhaled histamine in 16 patients with allergic rhinitis was compared with placebo on two consecutive days in a double-blind, crossover design. The PC15FEV1 was significantly increased one hour after treatment with vitamin C but not after placebo.

In 95 patients with severe chronic airway obstruction (FEV1 33.2 +/- 12% of predicted; mean +/- SE), we investigated whether drug therapy had any influence on serum Mg levels. 11/95 patients had a serum Mg less than 1.45 mEq/l (lower normal limit). Multiple-regression analysis showed that the use of diuretics was associated with a significantly lower serum Mg level (1.59 +/- CI 0.06 mEq/l vs. an adjusted mean of 1.71 mEq/l; F = 11, 2, p less than 0.001). There was a significant negative correlation between serum Mg and the length of oral steroid therapy (1.64 +/- CI 0.02 mEq/l for less than 24 months of therapy vs. 1.52 +/- CI 0.06 mEq/l for greater than 24 months of therapy; F = 7, 3, p less than 0.005). No effect of theophylline, inhaled steroids or beta 2-agonists on serum Mg was observed. Because of potential negative effects of hypomagnesemia on respiratory function, routine serum magnesium determination is recommended in patients with chronic obstructive lung disease taking diuretic drugs or corticosteroids.

To the Editor: The hepatopulmonary syndrome, which is characterized by hypoxemia due to intrapulmonary shunting or a ventilation-perfusion mismatch (or both), develops in some patients with liver cirrhosis. Patients with this syndrome have no apparent parenchymal lung disease but may have orthodeoxia, the unusual finding of increased hypoxemia with the change from a supine to a standing position.1 Increased endogenous production of nitric oxide may play a part in the hyperdynamic circulation that is typical of patients with the hepatopulmonary syndrome. An increased concentration of exhaled nitric oxide has recently been reported in one such patient; hypoxemia resolved and the . . .

To investigate the effects of air pollution on the respiratory health of children, a subject of some controversy, a comparative study was undertaken of 2,385 school children who lived in central urban, peripheral urban, and suburban areas. Daily monitoring of sulphur dioxide and total suspended particle concentrations in all areas showed that pollutant concentrations in central and peripheral urban areas were above commonly accepted safety levels for respiratory health, while concentrations in the suburban area were within acceptable limits. A questionnaire administered to each mother assessed environmental exposure to pollutants in the household, the occurrence of respiratory symptoms as well as lung diseases as diagnosed by a physician, and general information. Children were interviewed about smoking habits and any acute respiratory symptoms. Children also performed standard lung function tests. Results showed that children from both urban areas had lessened pulmonary function and a higher prevalence of bronchial secretion with common colds than did those from the suburban area. These differences persisted after corrections for exposure to indoor pollutants, active or passive smoking, socioeconomic status, and sex. Parental cigarette smoking was related to a fall in forced expiratory volume in 1 second and an increased incidence of acute respiratory illnesses and chronic cough in children. Although boys had higher lung volumes and lower air flow, regression analysis showed no significant influence of the interactions "sex-geographic area" and "sex-smoking" on lung function. It was concluded that air pollution has a significant effect on the respiratory health of children.

Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and maximal expiratory flow at 50% of FVC (MEF50) were measured in 1,880 school children who lived in urban areas before and after a decrease of air pollution. A group of 162 children from a suburban area served as controls. In the first survey, FEV1.0, FEF25-75, and MEF50 of children from urban areas were significantly lower, while in the second survey they were not significantly different from those of controls. The slopes over time of FEV1.0, FEF25-75, and MEF50, adjusted for sex and anthropometric variables, were closely related to the decrease of pollutants concentration. Our results suggest that a decrease of air pollution may produce an improvement of lung function.

Scintigraphy is currently the most widely used and most reliable diagnostic instrumental test for the diagnosis of osteoid osteoma. Indications for its use are based on two considerations: 1) the need for preoperative confirmation of a suspected diagnosis based on clinical and radiographic findings; 2) the preoperative differential diagnosis from lesions which, either due to site or to atypical features, can mimic osteoid osteoma and are not easily identified. However, the high sensitivity of the test is associated with low specificity. In order to increase the specificity, the authors use angioscintigraphy and illustrate some cases where this method permitted differential diagnosis with other bone lesions that simulate the clinical and radiographic features of osteoid osteoma.

Aims of our study were: to evaluate small airway function of subjects with past or present silica dust exposure and normal spirometric values; to investigate whether small airway disease is related to radiographic signs of silicosis, to cumulative dust exposure (ES) and to cigarette smoking. Maximal expiratory flow at 50% (MEF50) and 25% (MEF25) of forced expired vital capacity were measured in 112 subjects, 69 with radiographic signs of silicosis, group I, and the remaining 43 with normal chest X-rays. Even if age and ES were significantly higher in group I, no significant difference in respiratory function tests and in prevalence of small airway disease was found between the two groups. In both groups small airway function was significantly negatively related to smoking habits, while it was independent of the other variables considered. Multiple regression analysis with MEF50 and MEF25 as dependent variables did not show any significant relationship. We conclude that small airway disease due to encroachment of bronchiolar walls by SiO2 deposition is masqued by the damage produced by cigarette smoking, even in the presence of radiographic signs of silicosis.

The AA. report an unusual case of intraarticular osteoid osteoma of the elbow. Therefore the lesion was strongly suspected; the diagnosis was made only one year after the onset of symptoms by the use of Tc99m MDP bone scan specifically on the blood-pool image. Two earlier bone scans were made with negative results. Considerations have been made by the AA. on the metabolic behaviour of the tumor as shown by scintigraphic scans.

Mucosal oedema and airway hyperreactivity are common features of asthma, in which they seem to share a common pathogenesis, i.e. airway inflammation. The relationship between oedema and hyperreactivity has not yet been properly investigated. Some speculations are advanced, based on the available experimental evidence. Mucosal oedema may amplify bronchial responsiveness by increasing epithelial permeability, by altering airway mechanics, or by stimulating neural pathways. On the other hand, bronchoconstriction may contribute to oedema by increasing hydrostatic pressure in postcapillary venules.

Two groups of 10 patients with systemic arterial hypertension were studied by respiratory function tests before and after acute administration of diazoxide or furosemide. Small airways obstruction was present in a high percentage of patients and was partially reversed after the acute administration either of diazoxide or of furosemide. Systemic arterial hypertension seems to influence small airways caliber, through pulmonary vascular distension and/or pulmonary interstitial edema.

The acute effects of the intravenous administration of 10 mg verapamil on pulmonary function changes induced by rapid saline infusion were studied in six normal subjects. Rapid intravenous fluid overloading caused on increase of closing volume (from 6.55 +/- 1.74 to 9.53 +/- 1.77%, p less than 0.05). After verapamil, the closing volume did not increase after infusion in three subjects and the mean increase was not significant (7.08 +/- 1.82 to 8.43 +/- 1.86%). These results suggest that the rapid administration of intravenous verapamil blunts respiratory function abnormalities caused by overhydration interstitial lung oedema.

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in ten asthmatic patients with moderate to severe airway obstruction. Two grams of MgSO4 or saline in double-blind crossover design was administered IV for 20 minutes (0.40 mmol/min) and forced expiratory capacity and forced expiratory volume in one second (FEV1) were studied at intervals. Only at the end of MgSO4 infusion did FEV1 increase significantly (109% of initial values). The bronchodilating effect was short lasting and far less than that observed after salbutamol.

Tight junctions (TJ) play a major role in maintaining the integrity of epithelia. Damage of conducting airway surface epithelium is commonly observed in asthma, and recent data suggest that epithelial cells modulate airway smooth muscle tone by the production of relaxant factor(s). To evaluate the ultrastructure of tight junctions (TJ) in human bronchial epithelium of normal and diseased lung, biopsy samples were obtained by fiberoptic bronchoscopy in three normal healthy subjects, four asthmatic patients with bronchial hyperreactivity to methacholine and one heavy smoker with chronic bronchitis. Specimens were examined by electron microscopy, using both thin sections and freeze-fracture techniques. In normal subjects two types of TJ were identified, based on 27 type I, 23 type II junctional areas. Epithelium from the patient with chronic bronchitis showed extensive mucous metaplasia and only junctions of the second type. Extensive epithelial damage was detected in asthmatic subjects, so that a few TJ could be found. Varying degrees of TJ abnormalities were observed and the possible role of such ultrastructural derangements was discussed.

The authors take into consideration the ultrastructural aspects of osteoid osteoma and discuss the cellular and subcellular features of this neoplasm. Special attention is given to functional adaptability, which is specific for this type of cell, related to the degree of development of the neoformation.

A retrospective study of 561 patients with silicosis and 234 with asbestosis was performed to assess whether lung function decline in five years is related to the type (restrictive or obstructive) and/or to the degree of initial damage. Based on lung function tests, three groups of patients were identified: NC with normal lung function tests, CR with restrictive impairment and CO with airway obstruction. The degree of impairment was classified as mild, moderate and severe. Patients were considered worse if five years later they presented a higher degree of impairment. The prevalence of CR was significantly higher in asbestosis, that of NC and CO in silicosis (p less than 0.01). Among subjects with normal starting lung function, 9% only developed CR or CO 5 years later. The prevalence of subjects with worsened lung function in the CR groups was significantly higher (p less than 0.001) in asbestotics (36%) than in silicotics (14%) and was closely related to starting functional impairment. In the CO group the prevalence of worsened subjects was significantly higher than in CR (p less than 0.001), similar in the two diseases and independent of starting lung impairment.

The effects of inhaled MgSO4 on histamine bronchoprovocation test (BPT) were studied in nine asthmatics in clinical remission (FEV1 greater than 80% of predicted). Patients performed histamine BPT on 2 separate days, one day after saline and the other after MgSO4 inhalation, in a randomized double-blind design. Spirometry and flow/volume curve were recorded on each test day before and 5 min after NaCl or MgSO4. No significant difference was observed in lung function measurements 2 days before and after either NaCl or MgSO4. The dose of histamine which produced a 20% decrease in control FEV1 (PD20FEV1) was significantly increased by aerosolized MgSO4 (from 0.177 +/- 0.036 mg after NaCl to 0.350 +/- 0.085 after MgSO4, P less than 0.05. After MgSO4 the dose-steps of histamine concentration increased two-fold in two subjects and one-fold in five.

Nitric oxide may be involved in the impaired oxygenation of cirrhotic patients, a condition that improves in most patients after liver transplantation.To compare oxygenation and nitric oxide concentrations before and after liver transplantation.Before-and-after observational study.Academic medical center.18 patients with cirrhosis and no obvious cardiopulmonary disease who underwent successful orthotopic liver transplantation.Orthotopic liver transplantation.Blood gas analysis, measurement of exhaled nitric oxide, contrast-enhanced echocardiography, and pulmonary function tests.Before transplantation, the mean (+/- SD) exhaled nitric oxide concentration was higher in patients than in normal controls (13 +/- 4.9 parts per billion [ppb] compared with 5.75 +/- 1.9 ppb; P0.001). After transplantation, the alveolar-arterial oxygen gradient significantly decreased (from 17.3 +/- 7.1 mm Hg to 9 +/- 5.2 mm Hg; P0.001), as did the exhaled nitric oxide concentration (from 13 +/- 4.9 ppb to 6.2 +/- 2.8 ppb; P0.001). The decrease in the exhaled nitric oxide concentration was significantly correlated with the decrease in the alveolar-arterial oxygen gradient (r = 0.56; P = 0.014). Five patients met the criteria for the diagnosis of the hepatopulmonary syndrome before transplantation; the syndrome was cured by transplantation.The correlation between the decrease in exhaled nitric oxide concentration after liver transplantation and the improvement in oxygenation reinforces the hypothesis that nitric oxide is an important mediator of impaired oxygenation in patients with cirrhosis.

Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo2) to hypoxemia, is commonly present in patients with cirrhosis. Nitric oxide (NO), through pulmonary vasodilatation, may play a major role in the oxygen abnormalities of cirrhosis. Our aim was to study the relationship between NO production and O2 abnormalities in 45 nonsmoking patients with cirrhosis and without major cardiovascular and respiratory diseases. Intrapulmonary shunting was detected by contrast-enhanced (CE) echocardiography. Lung volumes and diffusion, arterial blood gas analysis, serum NO2-/NO3-, NO output in the exhaled air, and cardiac index by the echocardiographic method were determined in all patients. Twenty-seven (60%) patients had an abnormally increased (15 mm Hg) AaDo2. The mean values of exhaled NO output and serum NO2-/NO3- were significantly higher in cirrhotic patients than in controls (252 +/- 117 vs. 75.2 +/- 19 nL/min/m2, P.0001; and 47.5 +/- 29.4 vs. 32.9 +/- 10.1 micromol/L, P.02, respectively). In all patients, there was a significant correlation between exhaled NO and AaDo2 (r = .78, P.0001). Twelve patients (26.6%) were found to have CE-echocardiographic evidence of intrapulmonary shunting (positive CE-echo). Nine patients were considered to have hepatopulmonary syndrome (HPS) on the basis of an AaDo215 mm Hg and positive CE-echo. These 9 patients had a mean value of exhaled NO significantly higher than patients without HPS (331 +/- 73.2 vs. 223 +/- 118.4 nL/min/m2, P.05). In all patients, cardiac index was positively correlated with exhaled NO (r = .47, P.001) and with serum NO2-/NO3- (r = .43, P.01). The results suggest an important role of NO in the oxygenation and circulatory abnormalities of patients with cirrhosis.