Effects of topical low-dose preservative-free hydrocortisone on intraocular pressure in patients affected by ocular surface disease with and without glaucoma.

PURPOSE: This study aims to investigate the safety and efficacy of short-term treatment for ocular surface disease (OSD) with topical low-dose (1,005 mg) preservative-free hydrocortisone in one hundred patients with and without glaucoma. METHODS: This was an open label non-randomized clinical trial. Patients with OSD with and without primary open-angle glaucoma (POAG) received topical low-dose (1,005 mg) preservative-free hydrocortisone twice daily in each eye for 2 weeks. All patients underwent a complete ophthalmological examination at baseline (T0) and at 1 (T1) and 2 (T2) weeks post-treatment. At each visit, the intraocular pressure (IOP) and the ocular surface disease index (OSDI) questionnaire scores were recorded; the Schirmer test was performed only at T0 and T2. RESULTS: The OSDI score significantly decreased in both the POAG and no-POAG groups (both p < 0.0001) after hydrocortisone treatment, with no difference between the two groups (p = 0.72). There were no significant differences in IOP and Schirmer test results between T0 and T2 in both treatment groups (p = 0.68 and p = 0.83, respectively). CONCLUSIONS: Topical low-dose (1,005 mg) preservative-free hydrocortisone is safe and effective for improving OSD symptoms both in patients with and without POAG. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov under NCT04536129 on 01/09/2020 ("retrospectively registered").

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

SERUM YKL-40 IN CHILDREN WITH ASTHMA.

Asthma is one of the most common chronic diseases in children. To date the diagnosis of asthma is mainly clinical, based on the clinical history, a careful physical examination and lung function tests. However, symptoms are often not specific and lung function tests are not very sensitive. In order to find a solution to this problem new biomarkers of airway inflammation are being developed. YKL-40 is a chitinase-like protein that has a role in the inflammation and tissue remodeling in several human diseases. The aim of this study is to evaluate serum levels of YKL40 in children with intermittent or persistent asthma. We performed a cross-sectional analysis of serum samples from a cohort of patients with asthma and healthy controls. Patients with asthma were stratified according to four levels of asthma severity (mild intermittent, mild persistent, moderate persistent, and severe persistent). The analysis of serum samples was performed with the use of a commercially available enzyme-linked immune-adsorbent assay (ELISA) kit (Quidel). The minimum detection limit of the assay for YKL-40 is 15.6 ng per milliliter (ng/ml). Our data showed that circulating YKL-40 levels are significantly higher in patients with asthma than healthy subjects (36±18.6 vs 14:41±2.88, p= 0.001). Furthermore, we found significantly higher values of YKL-40 in both groups of children with intermittent asthma (p less than 0.001) and persistent asthma (p less than 0.001) than healthy controls. However, no correlation was found with duration and severity of asthmatic disease (r = 0:18, p= 0:33, r = 0.28 P = 0:13, respectively). Our data allow us to suggest that YKL-40 represents a useful biomarker of asthma in children with intermittent or persistent asthma.

SAFETY AND EFFICACY OF SUBLINGUAL SPECIFIC IMMUNOTHERAPY TO HOUSE DUST MITE USING A DIFFERENT DOSAGE: A PILOT STUDY.

The aim of this randomized open study was to evaluate the safety and efficacy of different dosages (2000 UI vs 4000 UI) of sublingual immunotherapy (SLIT) in patients with allergic diseases such as asthma associated to rhinitis and rhinoconjunctivitis sensitized to house dust mites. We enrolled 61 patients with a history of allergic asthma, and a positive skin prick test for Dermatophagoides (D.) pteronyssinus/farinae. Patients were randomly assigned to receiving SLIT at dosage of 2000 UI (Group A) or 4000 UI (Group B) maintenance dose. We evaluated: subjective symptoms using a Visual Analogic Scale (VAS), the amount of prescribed symptomatic drugs, bronchial reactivity to methacoline and side effects using a specific questionnaire. A significant improvement in symptoms, assessed by VAS, was observed with both SLIT doses with no significant differences between groups. The provocation dose of methacoline inducing a 20% fall of FEV1 significantly increased after 12 months only in the 4000 UI dose group. In conclusion, both monomeric allergoid dosages of SLIT (2000 UI and 4000 UI) are a safe and efficacy option to reduce symptoms in patients with allergic asthma caused by house dust mites. Moreover, both dosages are efficacious even to protect against airway reactivity but it seems that monomeric allergoid of SLIT at higher dosage (4000 UI) is better than at the lower dosage (2000 UI).

SERUM AND BAL YKL-40 LEVELS IN DIFFERENT INFLAMMATORY LUNG DISEASES: AN UPDATE.

YKL-40 (also called chitinase 3-like-1 or human cartilage glycoprotein 39) is a chitinase-like protein belonging to the family 18 of glycosyl hydrolase (GH18). This protein is involved in the inflammatory process acting as pro-inflammatory cytokine secreted by neutrophils, activated human macrophages, vascular smooth muscle cells and cancer cells. It has been shown that YKL-40 has a role in pathological tissue remodeling and development of fibrosis of several diseases. To date, the biological and pathophysiological function of YKL-40 protein in pulmonary diseases is still unclear. This review focuses on the role of YKL-40 in diagnosis and monitoring of different lung diseases in order to assess whether this protein could be used as biomarker of specific conditions featured by inflammation and fibrosis. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1997. The literature search was undertaken in October 2014.

RELATION OF BODY MASS INDEX WITH IgE LEVELS, ALLERGIC SENSITIZATION AND LUNG FUNCTION IN ASTHMATIC CHILDREN: OUR EXPERIENCE AND REVISION OF LITERATURE.

In recent decades, there has been an increase in the prevalence of asthma and obesity in pediatric age. In this regard several studies have provided controversial data to demonstrate the link between Body Mass Index (BMI) and asthma, both in adults and in children. In this prospective study we evaluated the relationship between body mass index value, total IgE immunoglobulin E levels, skin prick test (SPT) sensitization and lung function in children affected by asthma. According to the analysis of data on the comparison of normal-weight patients versus overweight/obese patients, there was no significant difference in the values of FEV1 (86%±12 vs 90%±19), FVC (81%±11 vs 88%±18), skin prick tests (22.72% vs 36.66%) and total IgE values (192.22±368.28 vs 503±914.04). We carried out a sub-analysis to study the difference between three groups of patients: normal weight, overweight and obese. Obese patients showed higher total IgE values than normal-weight patients with a statistically significant difference. Conversely, there was no significant difference between the normal weight group and the obese group in the respiratory function tests and the SPT. Moreover, we found a higher value of total IgE in female overweight/obese compared with normal weight, while there was no significant difference in relation to parameters of lung function and SPT. However, the same analysis in the male sample did not show any statistically significant difference. This study confirms the higher incidence of atopy in obese children, especially in female gender, but not a direct relationship with either allergens sensitization or abnormal lung function.

Neurotrophic keratitis.

Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervations, leading to a reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism and mitosis of epithelial cells, with subsequent deficiency in epithelial repair, stromal and intracellular oedema, loss of microvilli, and abnormal development of the basal lamina. Several recent studies have proposed different therapies based on different aetiopathogenetic theories. The aim of the therapy is to treat aetiopathogenesis and, at the same time, promote corneal healing. In this paper, we report the aetiology, diagnosis, management, and medical and surgical treatment of NK, also indicating future treatments based on the most recent studies.

Argas (Persicargas) persicus (Oken, 1818) (Ixodida: Argasidae) in Sicily with considerations about its Italian and West-Mediterranean distribution.

Recently, in the province of Trapani (Western Sicily), some overwintering specimens of the argasid tick Argos (Persicargas) persicus (Oken, 1818) were observed and collected. Morphological and genetic analysis were utilized in order to reach a definitive identification. The species was found in two semi-natural sites where, having been found repeatedly, its presence does not appear accidental. Moreover the characteristics of the Sicilian findings seem to exclude a human-induced spread. This record, the first regarding Sicily and South Italy, is discussed together with the previous doubtful citations for Italy. These findings revalue not only all the old citations for Italy but also the hypothesis that the Mediterranean distribution of this argasid is of a natural origin.

Chest wall kinematics during chemically stimulated breathing in healthy man.

Chest wall compartment kinematics and respiratory muscle coordinate activity, during either hypercapnia or hypoxia, have not been comparatively assessed in healthy humans. We assessed the displacement volume of the chest wall (Vcw) in 5 normal subjects during hypoxic-normocapnic and hypercapnic-hyperoxic rebreathing by using linearized magnetometers. Vcw was divided into displacement volumes of the rib cage (Vrc) and the abdomen (Vab). Esophageal (Pes) and gastric (Pga) pressures were simultaneously recorded and transdiaphragmatic pressure (Pdi) was calculated by subtracting Pes from Pga. Pressure swings (sw) from end expiration (EE) to end inspiration (EI) were also calculated. During both hypoxia and hypercapnia, from quiet breathing to 40 L/min VE, Vrc,EI increased consistently but Vrc,EE, and Vab,EI did not. Moreover, Vab,EE decreased significantly during hypercapnia and remained unchanged during hypoxia. PesEI decreased (more negative values) and PesEE increased (less negative values) during either stimulus, while PgaEE increased with hypercapnia. Pdisw, calculated as the difference between PdiEE and PdiEI, increased significantly with both hypercapnia and hypoxia ( p = 0.002 for both). On the plot of Pes vs Pga, the slope of a line from end expiratory to end inspiratory lung volume between 20 and 40 L/min VE progressively increased during hypercapnia indicating increasing rib cage muscle (RCM) contribution to inspiratory pressure swings relative to the diaphragm. From these results we conclude that in healthy man: (i) with both chemical stimuli RCM contribution accounts for increase in Vrc displacement; (ii) with hypercapnia, the decrease in Vab,EE displacement indicates abdominal muscle (ABM) contribution to tidal volume; (iii) RCM and ABM assist the diaphragmatic function during hypercapnic stimulation.

Respiratory dynamics during laughter.

Lung and chest wall mechanics were studied during fits of laughter in 11 normal subjects. Laughing was naturally induced by showing clips of the funniest scenes from a movie by Roberto Benigni. Chest wall volume was measured by using a three-dimensional optoelectronic plethysmography and was partitioned into upper thorax, lower thorax, and abdominal compartments. Esophageal (Pes) and gastric (Pga) pressures were measured in seven subjects. All fits of laughter were characterized by a sudden occurrence of repetitive expiratory efforts at an average frequency of 4.6 +/- 1.1 Hz, which led to a final drop in functional residual capacity (FRC) by 1.55 +/- 0.40 liter (P < 0.001). All compartments similarly contributed to the decrease of lung volumes. The average duration of the fits of laughter was 3.7 +/- 2.2 s. Most of the events were associated with sudden increase in Pes well beyond the critical pressure necessary to generate maximum expiratory flow at a given lung volume. Pga increased more than Pes at the end of the expiratory efforts by an average of 27 +/- 7 cmH2O. Transdiaphragmatic pressure (Pdi) at FRC and at 10% and 20% control forced vital capacity below FRC was significantly higher than Pdi at the same absolute lung volumes during a relaxed maneuver at rest (P < 0.001). We conclude that fits of laughter consistently lead to sudden and substantial decrease in lung volume in all respiratory compartments and remarkable dynamic compression of the airways. Further mechanical stress would have applied to all the organs located in the thoracic cavity if the diaphragm had not actively prevented part of the increase in abdominal pressure from being transmitted to the chest wall cavity.

The diaphragm and dyspnea during chemically stimulated breathing in a subset of patients with diabetes.

In patients with insulin-dependent diabetes mellitus (IDDM) isolated peripheral airway involvement may give rise to inspiratory threshold load (ITL) contributing to dyspnea. Based on the reported evidence of a greater increase in end-expiratory lung volume (EELV) with hypoxia than with hypercapnia in IDDM, we wondered whether, and to what extent in the two conditions, EELV contribute to perception of dyspnea (PD). We studied five nonsmokers aged between 19 and 45, with IDDM under good metabolic control and five normal control subjects matched for age. In each patient, we evaluated the electromyographic activity of the diaphragm (Edi), the swings of esophageal (Pessw), gastric (Pgsw), and transdiaphragmatic (Pdisw = Pgsw-Pessw) pressures; PD was assessed by a modified Borg scale during hypercapnic-hyperoxic (HCH) and hypoxic-isocapnic (HIC) stimulation. Change in inspiratory capacity (IC) was considered the mirror image of increase in EELV, that is, dynamic hyperinflation (DH), while intrinsic positive end inspiratory pressure (PEEPi) was measured as an index of inspiratory threshold load (ITL). In controls, Edi and Pdi but not their ratio (Edi/Pdi) related to Borg. In patients the following was found: (1) with each of the two stimuli, for any given Edi, Pdi, and Edi/Pdi ratio, there was greater Borg than in controls, (2) a similar increase in ITL and DH with HCH and HIC, (3) Edi/Pdi related to Borg similarly with HCH as with HIC. In conclusion, in controls, Edi and Pdi were associated with the perception of dyspnea similarly with the two chemical stimuli. In this subset of patients with IDDM, Edi/Pdi ratio throughout increase in EELV and ITL was found to affect the perception of dyspnea in hypoxia to a similar extent as in hypercapnia.

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.

The influence of metam sodium on soil respiration.

A laboratory experiment was performed in order to evaluate the extent to which metam sodium (MS) applied at two different recommended rates and its degradation product, methyl isothiocyanate (MITC), affect soil respiration. Results suggest that MS degradation to MITC was complete within 4 hours and that MITC decomposed quickly in a few days, except in the soil containing high organic matter where it was still present after 15 days. Following the addition of MS, a lag phase appeared in CO2-C evolution in the soil. It was longer for the higher dose of MS added and for the two soils with low organic C content. The dynamics of the process was described by the Bonde and Rosswall model and by the Gompertz RS E model for the untreated and the MS-treated soils, respectively.

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.

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.

Chest wall hyperinflation during acute bronchoconstriction in asthma.

The mechanics of the chest wall was studied in seven asthmatic patients before and during histamine-induced bronchoconstriction (B). The volume of the chest wall (VCW) was calculated by three-dimensional tracking of 89 chest wall markers. Pleural (Ppl) and gastric (Pga) pressures were simultaneously recorded. VCW was modeled as the sum of the volumes of the pulmonary-apposed rib cage (VRC,p), diaphragm-apposed rib cage (VRC,a), and abdomen (VAB). During B, hyperinflation was due to the increase in end-expiratory volume of the rib cage (0.63 +/- 0.09 L, p < 0.01), whereas change in VAB was inconsistent (0.09 +/- 0.07 L, NS) because of phasic recruitment of abdominal muscles during expiration. Changes in end-expiratory VRC,p and VRC,a were along the rib cage relaxation configuration, indicating that both compartments shared proportionally the hyperinflation. VRC,p-Ppl plot during B was displaced leftward of the relaxation curve, suggesting persistent activity of rib cage inspiratory muscles throughout expiration. Changes in end-expiratory VCW during B did not relate to changes in FEV(1) or time and volume components of the breathing cycle. We concluded that during B in asthmatic patients: (1) rib cage accounts largely for the volume of hyperinflation, whereas abdominal muscle recruitment during expiration limits the increase in VAB; (2) hyperinflation is influenced by sustained postinspiratory activity of the inspiratory muscles; (3) this pattern of respiratory muscle recruitment seems to minimize volume distortion of the rib cage at end-expiration and to preserve diaphragm length despite hyperinflation.

Respiratory muscle function and hypoxic ventilatory control in patients with type I diabetes.

STUDY OBJECTIVES: The interaction among pulmonary mechanics, respiratory muscle performance, and ventilatory control in subjects with insulin-dependent diabetes mellitus has so far received little attention. We therefore decided to assess the role of central factors and peripheral factors on the ventilatory response to a hypoxic stimulus in type I diabetic patients. SUBJECTS: Eight patients in stable condition aged 19 to 48 years old, with insulin-dependent diabetes mellitus (duration of the disease, 36 to 240 months) and no history of smoking, cardiopulmonary involvement, or autonomic neuropathy; and an age- and gender-matched control group. MEASUREMENTS: In each patient, we measured the following: pulmonary volumes; diffusing capacity of the lung for carbon monoxide (D(LCO)); time and volume components of ventilation (tidal volume [V(T)] and respiratory frequency); static compliance (Clstat) and dynamic compliance (Cldyn); swings in pleural pressure (Pes) and gastric pressure (Pg); and transdiaphragmatic pressure (Pdi), obtained by subtracting Pes from Pg. Maximal inspiratory Pes and Pdi during a maximal sniff maneuver were also measured. Swings in Pes and Pdi during V(T) as a percentage of Pes and Pdi during the maximal sniff maneuver [Pessw(%Pessn) and Pdisw(%Pdisn), respectively] were both considered as a measure of central respiratory output, and the Pessw(%Pessn)/V(T) ratio was considered as an index of neuroventilatory dissociation (NVD) of the inspiratory pump. Subjects were studied at baseline and during hypoxic rebreathing. RESULTS: Pulmonary volumes and D(LCO) were normal or slightly reduced. A lower Cldyn, higher central respiratory output, and NVD were found. During hypoxic rebreathing, patients had lower V(T), similar central respiratory output, and greater NVD per unit change in arterial oxygen saturation compared with values in control subjects. An increase in dynamic elastance, computed as 1/Cldyn, during hypoxia was found in patients, but not in normal subjects, and was directly related to concurrent changes in NVD. CONCLUSIONS: We have shown that the assessment of a normal Clstat and normal routine parameters of airway obstruction does not permit the definite exclusion of the role of peripheral airway involvement in insulin-dependent diabetes mellitus. Peripheral airway involvement is likely to influence indices of hypoxic ventilator) drive by modulating a normal central motor output into a rapid and shallow pattern of ventilatory response.

Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with type I diabetes mellitus under good metabolic control.

Dyspnoea and pulmonary dysfunction have recently been associated with Type I (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary mechanics and of performance of inspiratory muscles in inducing dyspnoea has not been yet assessed in Type I diabetes. To better focus on this topic we evaluated nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and stable metabolic control, without a history of smoking and microvascular complications, alongside a group of 14 healthy control subjects. In each subject, pulmonary volumes, static and dynamic compliance, pleural pressure swings (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of respiratory muscle effort, and tension-time index [TTI=TI/TTOTxPplsw(%Pplsn)] were measured (TI=inspiratory time;TTOT=total time of the respiratory cycle). All subjects were studied at baseline and during hypoxic rebreathing. Patients had normal pulmonary volumes. During hypoxic rebreathing, a normal change in respiratory muscle effort [DeltaPplsw(%Pplsn)/DeltaSaO2] and DeltaTTI/DeltaSaO2, and a lower change in tidal volume versus change in oxygen saturation [DeltaVT(% vital capacity)/DeltaSaO2], resulted in a higher ratio of respiratory effort to tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified Borg scale, showed a greater rate of rise (DeltaBorg/DeltaSaO2) and a greater increase for a given level of respiratory effort in patients. Moreover, neuroventilatory dissociation related to the expression of peripheral airway involvement, as assessed in terms of low dynamic compliance, and to concurrent change in dyspnoea sensation. Patients with Type I diabetes mellitus under good metabolic control and with normal lung volumes may have abnormal peripheral airway function. The latter is thought to be responsible for the association between dyspnoea sensation and neuroventilatory dissociation.

Methylmercury Resistance in Desulfovibrio desulfuricans Strains in Relation to Methylmercury Degradation.

Two strains of Desulfovibrio desulfuricans, one known to synthesize monomethylmercury from ionic mercury, were grown to determine methylmercury toxicity and for comparison with an anaerobic strain of Clostridium pasteurianum, a H(2) producer, and with the broad-spectrum mercury-resistant Pseudomonas putida strain FB-1, capable of degrading 1 mug of methylmercury to methane and elemental mercury in 2 h. The CH(3)HgCl resistance of D. desulfuricans strains was 10 times that of P. putida FB-1 and 100 times that of C. pasteurianum. The methylmercury resistance of D. desulfuricans was related to the disappearance of methylmercury from cultures by transformation to dimethylmercury, metacinnabar, methane, and traces of ionic mercury. During a 15-day experiment the kinetics of the two volatile compounds dimethylmercury [(CH(3))(2)Hg] and methane were monitored in the liquid by a specific new technique with purge-and-trap gas chromatography in line with Fourier transform infrared spectroscopy and in the headspace by gas chromatography with flame ionization detection. Insoluble metacinnabar (cubic HgS) of biological origin was detected by X-ray diffractometry in the gray precipitate from the insoluble residue of the pellet of a 1-liter culture spiked with 100 mg of CH(3)HgCl. This was compared with a 1-liter culture of D. desulfuricans LS spiked with 100 mg of HgCl(2). In a further experiment, it was demonstrated that insoluble, decomposable, white dimethylmercury sulfide [(CH(3)Hg)(2)S] formed instantly in the reaction of methylmercury with hydrogen sulfide. This organomercurial was extracted with chloroform and identified by gas chromatography in line with mass spectrometry. The D. desulfuricans strains were resistant to high concentrations of methylmercury because they produced insoluble dimethylmercury sulfide, which slowly decomposed under anaerobic conditions to metacinnabar and volatilized to dimethylmercury and methane between pHs 6.2 and 6.5 for high (4.5-g . liter) or low (0.09-g . liter) sulfate contents. Methane was produced from CH(3)HgCl at a lower rate than by the broad-spectrum Hg-resistant P. putida strain FB-1.