ADHD and eating disorders in childhood and adolescence: An updated minireview.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. However, little is still known about the association between ADHD and EDs through childhood and adolescence. Therefore, in the present work, we aimed at summarizing the studies investigating ADHD and EDs in childhood and adolescence over the last 10 years. METHODS: A bibliographic search on PubMed was performed and only studies that considered participants with a clinical diagnosis of ADHD, patients with an additional diagnosis of EDs and patients under 18 years old were included. A total of 7 studies were retrieved and included in the review. RESULTS: The majority of the reviewed studies (N = 5) found an association between ADHD and EDs, while the remaining, which focused on EDs symptomatology, reported either lower ED symptoms in ADHD sample or no association between ADHD and EDs. LIMITATIONS: the majority of studies were cross-sectional and therefore did not allow to explore the longitudinal casual relation between ADHD and EDs in the developmental age range considered. CONCLUSIONS: This review suggests that children and adolescents with ADHD should be monitored for EDs. However, more work is still needed to better understand the clinical implications of the comorbidity between ADHD and EDs and its prospective impact on the life of children and adolescents with ADHD.

Food web controls on mercury fluxes and fate in the Colorado River, Grand Canyon.

Mercury (Hg) biomagnification in aquatic food webs is a global concern; yet, the ways species traits and interactions mediate these fluxes remain poorly understood. Few pathways dominated Hg flux in the Colorado River despite large spatial differences in food web complexity, and fluxes were mediated by one functional trait, predation resistance. New Zealand mudsnails are predator resistant and a trophic dead end for Hg in food webs we studied. Fishes preferred blackflies, which accounted for 56 to 80% of Hg flux to fishes, even where blackflies were rare. Food web properties, i.e., match/mismatch between insect production and fish consumption, governed amounts of Hg retained in the river versus exported to land. An experimental flood redistributed Hg fluxes in the simplified tailwater food web, but not in complex downstream food webs. Recognizing that species traits, species interactions, and disturbance mediate contaminant exposure can improve risk management of linked aquatic-terrestrial ecosystems.

Caspofungin PK in critically ill patients after the first and fourth doses: suggestions for therapeutic drug monitoring?

We describe caspofungin pharmacokinetics (PK) after the first and fourth doses in 20 critically ill septic patients. Monte Carlo simulation was used to analyze the probability of target attainment (PTA) (AUC/MIC > 865) for Candida spp. Caspofungin concentrations were analyzed by HPLC in plasma and urine. A great variability in PK parameters was observed after both doses. Patients were divided in two groups according to their AUC values (AUC ≤ 75 mg h/L cut-off). In the low-AUC group Cmax, Cmin and AUC were lower, while Vd and Cl were higher than in the high-AUC group (p < 0.05, both at day 1 and 4). The mean 24-h urinary recovery of the drug was 8 ± 6.3% (day1) and 9.8 ± 6.3 (day4). Monte Carlo simulation analysis (0.03-1 mg/L MIC-range) showed that PTA was guaranteed only for MICs ≤ 0.03 mg/L in the low-AUC group, and for MICs ≤ 0.06 mg/L in the high-AUC group. No group had a PTA ≥ 90% for 0.125 mg/L MIC (the epidemiological cut-off). Mortality was higher in low-AUC group (p < 0.01). In our 'real-world' population, no clinical data can predict which patient will have lower, suboptimal caspofungin exposure, therefore we suggest TDM to optimize caspofungin therapy and reduce the risk of selecting resistances (CEAVC, 32366/2015; OSS.15.114, NCT03798600).

Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre.

BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF patients (66 male, mean age 78.3±23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. RESULTS: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p<0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.

Dyspnea, respiratory function and sputum profile in asthmatic patients during exacerbations.

Dyspnea is often used as a marker of asthma severity although a wide variation in dyspnea perception associated with bronchoconstriction (PB) has been described in asthmatic patients. Our hypothesis is that changes of airway inflammation, airway narrowing and hyperinflation may account for a part of the variability of breathlessness in spontaneous asthma attack. In asthmatic patients with exacerbation of the disease, we evaluated respiratory function, dyspnea (using visual Analogue Scale--VAS) and peak expiratory flow (PEF) values and variability (amplitude % mean), and sputum cellular and biochemical profile before (day I) and after (day II) therapy with i.v. corticosteroids and inhaled beta2-agonists, as appropriate. By day II, forced expiratory volume in 1 s (FEV1), inspiratory capacity (IC), PEF or VAS values and variability, sputum eosinophils and eosinophilic cationic protein (ECP) had improved. Improvement of dyspnea expressed as a decrease in VAS and reduction in variability of dyspnea sensation significantly correlated with increase in FEV1 %predicted value (%pv) (P=0.03; p=0.72 and P=0.02; p=0.74, respectively). No significant correlation was found between IC and VAS either in absolute values or as changes from days I and II, nor between sputum outcomes and PEF or VAS, regardless of how they were measured. We conclude that in acute asthmatic patients, dyspnea measurement, functional measurements and sputum analysis may be useful in monitoring disease activity, response to therapy and can provide different information on the state of the disease.

Perception of bronchoconstriction in smokers with airflow limitation.

To our knowledge, no data have been provided as to whether and to what extent dynamic hyperinflation, through its deleterious effect on inspiratory muscle function, affects the perception of dyspnoea during induced bronchoconstriction in patients with chronic airflow obstruction. We hypothesized that dynamic hyperinflation accounts in part for the variability in dyspnoea during acute bronchoconstriction. We therefore studied 39 consecutive clinically stable patients whose pulmonary function data were as follows (% of predicted value): vital capacity (VC), 97.8% (S.D. 16.0%); functional residual capacity, 105.0% (18.8%); actual forced expiratory volume in 1 s (FEV(1))/VC ratio, 56.1% (6.3%). Perception of dyspnoea using the Borg scale was assessed during a methacholine-induced fall in FEV(1). The clinical score and the treatment score, the level of bronchial hyper-responsiveness and the cytological sputum differential count were also assessed. In each patient, the percentage fall in FEV(1) and the concurrent Borg rating were linearly related, with the mean slope (PD slope) being 0.09 (0.06). The percentage fall in FEV(1) accounted for between 41% and 94% of the variation in the Borg score. At a 20% fall in FEV(1), the decrease in inspiratory capacity (Delta IC) was 0.156 (0.050) litres. Patients were divided into three subgroups according to the PD slope (arbitrary units/% fall in FEV(1)): subgroup I [eight hypoperceivers; PD slope 0.026 (0.005)], subgroup II [26 moderate perceivers; 0.090 (0.037)] and subgroup III [five hyperperceivers; 0.200 (0.044)]. By applying stepwise multiple regression analysis with the PD slope as the dependent variable, and other characteristics (demographic, clinical and functional characteristics, smoking history, level of bronchial hyper-responsiveness and sputum cytological profile) as independent variables, Delta IC (r(2)=45%, P<0.00001) and to a lesser extent treatment score (r(2)=17.3%, P<0.0006), and to an even lesser extent age (r(2)=3%, P<0.05), independently predicted a substantial amount (r(2)=65.27%, P<0.00001) of the variability in the Borg slope. Thus acute hyperinflation, and to a lesser extent treatment score and age, account in part for the variability in the perception of dyspnoea after accounting for changes in FEV(1) during bronchoconstriction in patients with chronic airflow obstruction.

Do inhaled corticosteroids affect perception of dyspnea during bronchoconstriction in asthma?

BACKGROUND: Some of the disagreements on the perception of dyspnea (PD) during bronchoconstriction in asthma patients could depend on the interrelationships among the following: (1) the influence of baseline airflow obstruction on the patient's ability to detect any further increase in airway resistance; (2) the effect of eosinophilic inflammation on the airway; (3) bronchial hyperresponsiveness (BHR); and (4) the effect of inhaled corticosteroids (ICSs). OBJECTIVE: We hypothesized that if the inflammation of the airway wall influences to some extent and in some way the PD in asthma patients, ICSs reverse the effect of airway inflammation on the PD. METHODS: We studied 100 asthma patients who were divided into the following four groups: patients with obstruction who were either ICS-naive (group I) or were treated with ICSs (group II); and nonobstructed patients who were either ICS-naive (group III) or were treated with ICSs (group IV). PD on the visual analog scale (VAS) was assessed during a methacholine-induced FEV(1) decrease and specifically was quantified as the VAS slope and score at an FEV(1) decrease of 5 to 20%. BHR was assessed in terms of the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). Eosinophil counts in induced sputum samples also were performed. Regression analysis, univariate analysis of variance, and factor analysis were applied for statistical evaluation. RESULTS: For a 5 to 20% fall in FEV(1) from the lowest point after saline solution induction, VAS score was lowest in group II, slightly higher in group I, slightly higher still in group IV, and the highest in group III. In the patients as a whole, BHR related to PD, but age, clinical score, duration of the disease, and presence of baseline airway obstruction did not. In patients with obstruction who were treated with ICSs, eosinophil counts related to PD negatively. Factor analysis yielded the following four factors that accounted for 70% of the variance in the data: ICS; eosinophil counts; FEV(1); and PC(20) loaded on separated factors with PD loading on the same factors as PC(20). The post hoc analysis carried out dividing the patients into ICS-treated and ICS-naive, showed that in the former group eosinophil counts and BHR proved to be factors negatively associated with PD, while in the latter group eosinophil counts were positively associated with PD. CONCLUSIONS: We have shown that eosinophilic inflammation of the airway wall may increase PD and that the association of eosinophil counts with ICSs may result in lessening the PD.

Pharmacological treatment of exercise dyspnoea.

A better understanding of the mechanisms of dyspnoea improves the clinician's ability to treat patients with shortness of breath. Any intervention that: 1) reduces ventilatory demands; 2) reduces ventilatory impedance; or 3) improves inspiratory muscle function, may relieve dyspnoea. Reduced ventilatory demand may be obtained by reducing metabolic load. Supplemental oxygen during exercise reduces exertional breathlessness and improves exercise tolerance, the decrease in dyspnoea being proportional to decrease in minute ventilation. Reduced ventilatory demand may also be obtained by decreasing the central drive. Opiates have been shown to decrease minute ventilation at rest and during submaximal exercise. They can alter the central processing of neural signals within the central nervous system to reduce sensations associated with breathing. Contrastingly, no consistent improvement in dyspnoea (versus placebo) has been shown with anxolytics. Decreasing central drive may also be obtained by altering pulmonary afferent information. Interventions that alter transmittal of afferent information to the central controller, potentially reduce dyspnoea. Reduction of ventilatory impedance is obtained by administering B2, anticholinergics or theophylline. B2 and anticholinergics act by modulating the increase in operational lung volumes and the inspiratory muscle effort during exercise. The mechanism by which theophylline relieves dyspnoea is probably related to a mechanism other than its bronchodilation alone. Alterations in respiratory muscle function are currently being detected in patients with chronic obstructive pulmonary disease, due to alteration in respiratory muscle energy balance. Nutritional repletion may improve respiratory muscle function but uncertainty remains as to whether nutritional repletion may relieve dyspnoea. The cumulative benefit of interventions targeting the pathophysiologic mechanism of dyspnoea must be identified for optimum treatment of patients with shortness of breath.

Relevance of dyspnoea and respiratory function measurements in monitoring of asthma: a factor analysis.

Previous studies in patients with stable chronic obstructive pulmonary disease have demonstrated that objective measures (lung volumes and respiratory muscle force) and clinical or subjective measures (symptoms of breathlessness and exercise tolerance) are quantities that independently characterize the conditions of these patients. Such an evaluation has not been previously applied in patients with stable bronchial asthma. Sixty-nine patients with stable chronic asthma underwent evaluation of static (functional residual capacity, FRC) and dynamic [forced expiratory volume in 1 sec (FEV1) and forced vital capacity, FVC] lung volumes; respiratory muscle strength (RMS), by measuring maximal inspiratory and expiratory pressures, and exercise capacity by means of the 6-min walking distance (6MWD). Chronic exertional dyspnoea was assessed by the Baseline Dyspnoea Index (BDI) focal score and by the Medical Research Council (MRC) scale. Statistical evaluation was performed by applying factor analysis. Three factors accounted for 78% of the total variance in the data: FEV1, FVC loaded on a factor I; RMS, FRC and 6MWD loaded on a factor II; dyspnoea ratings loaded on a factor III. Post-hoc analysis by randomly dividing the patients into two subgroups gave the same results. In asthmatic patients, airway obstruction appeared as an independent dimension or factor. Dyspnoea independently characterized the condition of asthma. Submaximal exercise tolerance could not be associated with the symptom of breathlessness. Evidence of independent factors support the validity of routine, multi-factorial assessment and the primary goal of treatment to alleviate symptoms and improve functional capacity in stable asthmatics.

Assessing inspiratory muscle strength in patients with neurologic and neuromuscular diseases : comparative evaluation of two noninvasive techniques.

STUDY OBJECTIVES: Static mouth pressure during maximal inspiratory efforts is commonly used to evaluate inspiratory muscle strength. However, maximal inspiratory pressure (MIP) presents some potential limitations likely to be overcome by the measure of mouth pressure during a maximal sniff maneuver in patients with respiratory muscle weakness. The aim of the present study was to assess whether mouth pressure during sniff maneuver (Pmosn) is a better index of inspiratory muscle strength than MIP in patients with neurologic and neuromuscular diseases (NNMD) with and without inspiratory muscle weakness. SUBJECTS AND MEASUREMENTS: Both MIP and Pmosn were measured in 30 patients affected by various types of NNMD and in 41 control subjects. Pmosn was measured with a 5-cm latex balloon-catheter system, the balloon being held in the oral cavity with the lips closed. RESULTS: In control subjects, MIP was either similar (in female subjects) or higher (in male subjects) than Pmosn, the variation coefficients for the two tests being similar both in male subjects (19.3% vs 19.1% for MIP and Pmosn, respectively) and in female subjects (27.5% vs 26.2%, respectively). There was no difference in the Pmosn/MIP ratios observed in the different diseases (one-way analysis of variance, F = 0.29, p = 0.91). In control subjects, a significant inverse relationship between Pmosn/MIP ratio and MIP (r = - 0.66, p < 0.00001) was found, ie, the lower the MIP, the higher the Pmosn/MIP ratio, suggesting an increasing difficulty in performing MIP as MIP values decreased. The majority of patients were between the prediction limits of the regression calculated for control subjects. At variance, patients with Duchenne dystrophy and low MIP were under the prediction limits of the regression calculated for control subjects, indicating a lower-than-expected PMOSN. CONCLUSIONS: In patients with NNMD, irrespective of the etiology, we found the following: (1) Pmosn does not overcome the limitations of MIP measurement; (2) the two maneuvers are not interchangeable, but rather complement one another in the assessment of inspiratory muscle strength; (3) Pmosn may underestimate muscle strength as assessed by MIP in patients with NNMD with inspiratory muscle weakness; and (4) in patients with low MIP, the lower-than-expected Pmosn/MIP ratio confirms inspiratory muscle weakness.

Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by the rearrangement of extracellular matrix and progressive increase in the amount of fibrotic tissue in the lung. IGF-I is a potent profibrogenic molecule and its bioavailability is dependent on at least 6 binding proteins called IGFBPs. Among these, IGFBP-3 is the most represented in serum and in different connective tissues. The purpose of this study was to identify and characterize IGFBP-3 in bronchoalveolar lavage (BAL) fluids. We studied 11 patients with IPF and 6 normal subjects by performing baseline pulmonary function test and BAL. IGF-I and IGFBP-3 were measured by RIA in BAL and serum. No significant differences were observed between serum IGF-I and IGFBP-3 from IPF patients and normal subjects. Instead, the direct measurement in BAL revealed a significant increase of IGF-I and IGFBP-3 in IPF patients compared to normal subjects. BAL IGF-I and IGFBP-3 concentrations were significantly related to inspiratory vital capacity (IVC) and carbon dioxide partial pressure (PaCO2): the higher the value of IVC and the lower the value of PaCO2, the higher the level of IGF-I and IGFBP-3. In conclusion, IGFBP3 and IGF-I could be important local mediators of IPF. Their direct measurement in BAL in IPF patients could be used as a clinical marker of the disease, since high levels of IGFBP-3 and IGF-I in BAL are associated to the initial phase of the disease.

Airway obstruction and chronic exertional dyspnoea in patients with persistent bronchial asthma.

In patients with COPD, flow limitation (FL) predicts chronic exertional dyspnoea (CED) better than routine spirometry. Whether, and to what extent, FL and CED are overlapping quantities in chronic asthma has not yet been defined. Forty consecutive clinically stable asthmatic patients without smoking history or cardiopulmonary disorders, were studied. In each subject respiratory function, including static and dynamic pulmonary volumes, was evaluated; maximal (MEFV) and partial (PEFV) expiratory V'-V curves and isovolumic partial to maximal flow ratio (M/P). FL was assessed in a seated patient by comparing tidal and PEFV curves; FL was detected when tidal flows were superimposed or exceeded those obtained during PEFV curves, and was expressed as a percentage of the expired control tidal volume (V(T)) affected by flow limitation (FL% VT). Dyspnoea was assessed by both MRC scale and Baseline Dyspnoea Index (BDI) focal score. Half of the patients were found to have FL. They were older, more dyspnoeic and more obstructed (P<0.03 - P<0.000005) than the non-FL group. FEV1, vital capacity (VC), age, body mass index, FL and M/P ratio were all related to dyspnoea scores. FL was significantly related to FEV1 (r = - 0.59). Multiple regression analysis showed that FEV1 (P=0.003, r2= 15-3% and P = 0.004, r2= 20.3%) and age (P = 0.0006, r2 = 26.8% and P = 0.016, r2 = 11%) independently predicted a part of the variance of MRC (P = 0.0001, r2 = 42.1%) and BDI (P = 0.0008, r2 = 31.3%), respectively. With dyspnoea scale being the gold standard, diagnostic accuracy (sensitivity and specificity) by ROC (receiver operating characteristics) analysis was similar for FEV1 and FL. The results indicate that FL may be present in this subset of asthmatics. CED may not be easily explained by abnormalities of routine spirometry or FL, the largest part of the CED variance remained unexplained. Thus, routine spirometry, FL and CED in patients with bronchial asthma are only partially overlapping quantities which need to be assessed separately.

Perception of bronchoconstriction and bronchial hyper-responsiveness in asthma.

The inter-relationship between the perception of bronchoconstriction, bronchial hyper-responsiveness and temporal adaptation in asthma is still a matter of debate. In a total of 52 stable asthmatic patients, 32 without airway obstruction ¿forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) 84.1% (S.D. 7.9%), and 20 with airway obstruction [FEV(1)/VC 60% (4%)], we assessed the perception of bronchoconstriction during methacholine inhalation by using: (i) the slope and intercept of the Borg and VAS (Visual Analog Scale) scores against the decrease in FEV(1), expressed as a percentage of the predicted value; and (ii) the Borg and VAS scores at a 20% decrease in FEV(1) from the lowest post-saline level (PB(20)). Bronchial hyper-responsiveness was assessed as the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)FEV(1)). The reduction in FEV(1) was significantly related to the Borg and VAS scores, with values for the group mean slope and intercept of this relationship of 0.13 (S.D. 0.08) and -1.1 (3.02) for Borg, and 1.5 (1.19) and -12.01 (35) for VAS. PB(20) was 3 (1.75) with Borg scores and 34.6 (20.5) with VAS scores. Compared with the subgroup without airway obstruction, the obstructed subgroup exhibited similar slopes, but lower Borg and VAS intercepts. For similar decreases in FEV(1) (5-20% decreases from the lowest post-saline values), the Borg and VAS scores were lower in the non-obstructed than in the obstructed subgroup. PC(20)FEV(1) was significantly related to both Borg PB(20) and VAS PB(20) when considering all patients. When assessing the subgroups, PC(20)FEV(1) was related to Borg PB(20) and VAS PB(20) in the non-obstructed subjects, but not in the obstructed subjects. In neither subgroup was the log of the cumulative dose related to the Borg and VAS scores at the end of the test. We conclude that, unlike in previous studies, the ability to perceive acute bronchoconstriction may be reduced as background airflow obstruction increases in asthma. Bronchial hyper-responsiveness did not play a major role in perceived breathlessness in patients without airway obstruction, and even less of a role in patients with obstruction. The cumulative dose of agonist did not appear to influence the perception of bronchoconstriction.

Hypoxic and hypercapnic breathlessness in patients with type I diabetes mellitus.

STUDY OBJECTIVES: The putative role of the performance of inspiratory muscles and breathing pattern in inducing dyspnea has been recently assessed during hypoxic stimulation in patients with type I diabetes (IDDM). Compared to a hypoxic stimulus, a hypercapnic stimulus, which may differently affect the pattern of breathing, could therefore modulate the coupling between respiratory effort and ventilatory output, which is involved in dyspnea sensation. SUBJECTS: Eight stable patients aged 19 to 48 years old, with IDDM (duration of disease, 36 to 240 months) and no smoking history, cardiopulmonary involvement, or autonomic neuropathy; and an age- and sex-matched control group. MEASUREMENTS: Pulmonary volumes, diffusing capacity of the lung for carbon monoxide, time and volume components (tidal volume [VT] and respiratory frequency), dynamic elastance (Eldyn), and swings in pleural pressure (Pessw) were measured. Maximal inspiratory pleural pressure (Pes) during a maximal sniff maneuver (Pessn), respiratory muscle effort or output (Pessw%Pessn), tension time index (TTI) = TI/total breathing cycle time x Pessw(%Pessn), and swing in Pes during VT as a percentage of Pessn were also evaluated. Dyspnea sensation was assessed by a modified Borg scale. Subjects were studied at baseline and during hypoxic and hypercapnic rebreathing tests. RESULTS: Compared to control subjects, patients exhibited normal routine spirometric function and Pessn, but a higher Eldyn, indicating peripheral airway involvement. In patients, but not in control subjects, Eldyn increased during both chemical stimuli and increased more during hypoxia than during hypercapnia. Also, changes in both VT and Pessw(%Pessn) on changes in PCO(2) were lower, while changes in Pessw(%Pessn)/VT, an index of neuroventilatory dissociation (NVD) of the ventilatory pump, on changes in PCO(2) were greater. Changes in VT and NVD for unit change in arterial oxygen saturation were lower and higher, respectively. Changes in Borg scale per changes in NVD were greater during both stimuli. Furthermore, compared to hypoxic conditions, a greater VT for any level of both minute volume and Pessw(%Pessn), and lower changes in Borg scale on changes in Pessw(%Pessn) and Pessw(%Pessn)/VT were found in hypercapnia. Changes in NVD and Borg scale related to changes in Eldyn with both chemical stimuli. CONCLUSIONS: In IDDM, the greater perception of dyspnea is associated with changes in inspiratory effort being out of proportion to changes in VT. The greater increase in Eldyn and the lower increase in VT may, in part, account for the greater perception of breathlessness during hypoxia.

Diagnostic accuracy of sputum outcomes in chronic stable asthma.

BACKGROUND: Asthma with non-remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders. OBJECTIVE AND METHODS: In order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis. RESULTS: Sputum eosinophils were above the normal range of our laboratory (0-3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 microg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and beta2-reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non-asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and beta2-reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively). CONCLUSION: Sputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.

Reduction in bronchodilation following a deep inhalation is poorly related to airway inflammation in asthma.

In patients with bronchial asthma, forced expiratory flows are differently sensitive to a previous volume history. A reduced ability of a deep inhalation (DI) to dilate obstructed airways has been hypothesized to be a physiological marker for the degree of airway responsiveness and to relate to the presence and magnitude of inflammation in the lung, even in mild stable asthma. However, there are at present doubts as to whether functional changes could be used as a substitute for airway inflammation studies. In order to investigate the interrelations among airway inflammation, bronchial hyperresponsiveness and effects of volume history, 58 consecutive asthmatics with mild to moderate asthma were studied. The effects of DI were assessed as the isovolumic ratio of flows from forced expiratory manoeuvres started from maximal (M) or partial (P) lung inflation. Airway inflammation was assessed by using induced sputum. Sputum was analysed for total and differential cell counts, and levels of eosinophil cationic protein (ECP) which reflects eosinophil activation. Airway responsiveness was assessed as the provocative concentration of histamine which caused a 20% fall in forced expiratory volume in one second (FEV1) from control (PC20). The M/P ratio was significantly related to ECP (r=-0.31, p<0.03) and eosinophils (r=-0.29, p<0.03), FEV1/vital capacity (VC) (r=0.32; p<0.01), clinical score (r=-0.33; p<0.03) and age (r=-0.41; p<0.0001). In a stepwise multiple regression analysis including age, score, baseline lung function, ECP, number of eosinophils and the response to beta2-agonist, age (p<0.037) predicted a small amount of the variance in M/P ratio (r2=0.12). It is concluded that volume history response is substantially independent of both sputum outcomes (inflammatory cell number and eosinophil cationic protein) and bronchial hyperresponsiveness; rather it seems to be associated with anthropometric characteristics. Functional aspects do not provide information on eosinophilic, probably central, airway inflammation.