Effects of saline nebulization on SARS-CoV-2 RNA spreading and exhaled bio-aerosol particles in COVID-19 patients.

BACKGROUND: Nebulized therapy is the mainstay for treating obstructive airway diseases, but there is heightened concern about the potential risk for SARS-CoV-2 transmission during nebulization in COVID-19 patients. AIM: To investigate the effects of 0.9% saline nebulization on SARS-CoV-2 RNA spreading in 11 COVID-19 patients (five females, mean age 62.45 ± 9.31 years); also to ascertain whether saline nebulization changed the number of exhaled bio-aerosol particles in six out of the 11 patients. METHODS: Air samples were collected using suction pumps equipped with 0.45 µm PTFE filters and positioned around the patient's bed. Exhaled particles were quantified by using an optical particle counter. FINDINGS: At baseline (i.e. before nebulization) SARS-CoV-2 was detected more frequently in the pumps close to the patient than in those far away. After saline nebulization, the detection of SARS-CoV-2 in the pumps close to the patient was comparable to that observed at baseline. In the pumps far from the patient, saline nebulization slightly, but not significantly, increased SARS-CoV-2 RNA detection compared to baseline. Overall, no significant changes in the SARS-CoV-2 RNA detection were observed after saline nebulization. At baseline, exhaled particle emission varied among patients, with two of them showing higher emission of particles than the remaining patients. Saline nebulization induced a marked decrease in exhaled particles in the two patients who displayed high emission at baseline, whereas no changes were observed in the remaining patients. Saline nebulization did not significantly change SARS-CoV-2 RNA spreading. CONCLUSION: Saline nebulization does not significantly increase SARS-CoV-2 spreading.

Relationship between hyponatremia at hospital admission and cardiopulmonary profile at follow-up in patients with SARS-CoV-2 (COVID-19) infection.

PURPOSE: Hyponatremia occurs in about 30% of patients with pneumonia, including those with SARS-CoV-2 (COVID-19) infection. Hyponatremia predicts a worse outcome in several pathologic conditions and in COVID-19 has been associated with a higher risk of non-invasive ventilation, ICU transfer and death. The main objective of this study was to determine whether early hyponatremia is also a predictor of long-term sequelae at follow-up. METHODS: In this observational study, we collected 6-month follow-up data from 189 laboratory-confirmed COVID-19 patients previously admitted to a University Hospital. About 25% of the patients (n = 47) had hyponatremia at the time of hospital admission. RESULTS: Serum [Na+] was significantly increased in the whole group of 189 patients at 6 months, compared to the value at hospital admission (141.4 ± 2.2 vs 137 ± 3.5 mEq/L, p < 0.001). In addition, IL-6 levels decreased and the PaO2/FiO2 increased. Accordingly, pulmonary involvement, evaluated at the chest X-ray by the RALE score, decreased. However, in patients with hyponatremia at hospital admission, higher levels of LDH, fibrinogen, troponin T and NT-ProBNP were detected at follow-up, compared to patients with normonatremia at admission. In addition, hyponatremia at admission was associated with worse echocardiography parameters related to right ventricular function, together with a higher RALE score. CONCLUSION: These results suggest that early hyponatremia in COVID-19 patients is associated with the presence of laboratory and imaging parameters indicating a greater pulmonary and right-sided heart involvement at follow-up.

Prevalence of nutritional risk and malnutrition during and after hospitalization for COVID-19 infection: Preliminary results of a single-centre experience.

BACKGROUND & AIMS: The effect of the COVID-19 infection on nutritional status is not well established. Worldwide epidemiological studies have begun to investigate the incidence of malnutrition during hospitalization for COVID-19. The prevalence of malnutrition during follow-up after COVID-19 infection has not been investigated yet. The primary objective of the present study was to estimate the prevalence of the risk of malnutrition in hospitalized adult patients with COVID-19, re-evaluating their nutritional status during follow-up after discharge. The secondary objective was to identify factors that may contribute to the onset of malnutrition during hospitalization and after discharge. METHODS: We enrolled 142 COVID-19 patients admitted to Careggi University Hospital. Nutritional parameters were measured at three different timepoints for each patient: upon admission to hospital, at discharge from hospital and 3 months after discharge during follow-up. The prevalence of both the nutritional risk and malnutrition was assessed. During the follow-up, the presence of nutritional impact symptoms (NIS) was also investigated. An analysis of the association between demographic and clinical features and nutritional status was conducted. RESULTS: The mean unintended weight loss during hospitalization was 7.6% (p < 0.001). A positive correlation between age and weight loss during hospitalization was observed (r = 0.146, p = 0.08). Moreover, for elderly patients (>61 years old), a statistically significant correlation between age and weight loss was found (r = 0.288 p = 0.05). Patients admitted to an Intensive Care Unit (ICU) or Intermediate Care Unit (IMCU) had a greater unintended weight loss than patients who stayed in a standard care ward (5.46% vs 1.19%; p < 0.001). At discharge 12 patients were malnourished (8.4%) according to the ESPEN definition. On average, patients gained 4.36 kg (p < 0.001) three months after discharge. Overall, we observed a weight reduction of 2.2% (p < 0.001) from the habitual weight measured upon admission. Patients admitted to an ICU/IMCU showed a higher MUST score three months after discharge (Cramer's V 0.218, p = 0.035). With regard to the NIS score, only 7 patients (4.9%) reported one or more nutritional problems during follow-up. CONCLUSIONS: The identification of groups of patients at a higher nutritional risk could be useful with a view to adopting measures to prevent worsening of nutritional status during hospitalization. Admission to an ICU/IMCU, age and length of the hospital stay seem to have a major impact on nutritional status. Nutritional follow-up should be guaranteed for patients who lose more than 10% of their habitual weight during their stay in hospital, especially after admission to an ICU/IMCU.

What drives inhaler prescription for asthma patients? Results from a real-life retrospective analysis.

BACKGROUND: The choice of inhaler device for asthma patients depends upon multiple attributes. We investigated factors that may drive general practitioners (GPs) and respiratory specialists in the prescription of inhaler devices for asthma patients who initiated inhalation therapy. METHODS: We retrospectively analysed prescriptions by GPs and respiratory specialists to asthma patients commencing inhaled corticosteroid/long-acting ß2-agonist combination therapy available as both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Patient characteristics were compared by device and multivariate analysis was used to model the likelihood of receiving a pMDI as opposed to a DPI in order to identify drivers for prescription. A sample of the respiratory specialists completed an ad-hoc survey of their perceived success in achieving asthma control in their patients and barriers to attaining full control. RESULTS: Prescription of a particular inhaler device was unrelated to the characteristics of the patients. Multivariate analysis revealed that the main driver for the choice of inhaler device was the medication (Odds Ratio and 95% Confidence Interval, respectively for GPs and specialists: 0.19 [0.16-0.23]; 0.17 [0.08-0.37]). Specialists perceived asthma as being inadequately controlled in 41% of their patients, and considered patients' difficulties in using DPIs and pMDIs as instrumental in this, citing a need for a novel, more effective inhaler technology. CONCLUSION: Physicians choose inhaler devices according to the prescribed drugs and not to the characteristics of the individual patient. This may reflect a lack of confidence in existing inhaler devices and underlines the need for technologies, which are more reliable and easier to use by patients.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals to each other and thence to patients. The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience. It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future. The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group.

Erratum: Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

[This corrects the article DOI: 10.1038/npjpcrm.2016.17.].

Prescription of inhalers in asthma and COPD: towards a rational, rapid and effective approach.

Inhaled medication is the cornerstone of the pharmacological treatment of patients with asthma and COPD. The major two classes of inhaled medication include corticosteroids (ICS) and bronchodilators. There is a wide diversity in molecules in both classes. Moreover, there is a wide variation in delivery systems. The correct use of inhalers is not granted and patients often incur in many mistakes when using pMDIs and DPIs, despite repeated instructions. A better matching between patient and device could be accomplished if the physician is aware of: (1) the patient characteristics (disease, severity, fluctuation in airflow obstruction, etc); (2) what class of medication is indicated; (3) where in the lung the medication should be delivered; and, (4) how this can be best achieved by a given device in this specific patient. We focus on the prescription of pMDIs and DPIs at the GP office or at the outpatient clinic of the hospital, and we propose an evidence based approach enabling the caregiver to make a rational choice in only a few minutes by just considering the following four simple questions: Who?, What? Where? and How? (the so-called 3W-H approach).

Motor features of voluntary cough following partial laryngectomy for glottal carcinoma.

BACKGROUND: Aspiration and respiratory tract infections are commonly observed in patients following conservative laryngeal surgery such as supracricoid laryngectomy with cricohyoidopexy (CHP). Since laryngeal closure is important for cough effectiveness, we hypothesised that CHP reduced cough intensity by affecting the cough motor pattern. METHODS: In ten male patients with laryngeal cancer eligible for CHP, we assessed the intensity of maximum voluntary cough (MVC) prior to and 2 months after surgery. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGp) and the ratio of IEMGp to the duration of the expiratory ramp during cough (TEC), i.e. the rate of rise of IEMG activity (IEMGp/ TEC). For each cough effort, the duration of the compressive phase (CP), the cough peak flow (CPF), the time elapsed from the onset of cough to CPF (TTP) and their ratio, i.e. the volume acceleration (VA), were also evaluated. RESULTS: CHP did not affect IEMG-related variables; in contrast, it reduced (p < 0.01) CPF, CP and lengthened (p < 0.05) TTP values. In consequence, cough VA values after CHP were consistently lower than in control condition. CONCLUSIONS: Supracricoid laryngectomy with CHP alters the intensity of voluntary cough as indexed by flow-related variables. This may reduce cough efficiency and facilitate the onset and/or persistence of chest infections (Tab. 2, Fig. 1, Ref. 22).

Retail sales of inhalation devices in European countries: so much for a global policy.

OBJECTIVE: To evaluate the retail sales of pressurised metered-dose inhalers (pMDIs), dry-powder inhalers (DPIs) and liquids for nebulisation in 16 European countries. METHODS: Retail sales data relating to pMDIs, DPIs and liquids for nebulisation delivering short- and long-acting bronchodilators, corticosteroids and combinations between 2002 and 2008 were obtained from the IMS sales database. The IMS database ensured that wholesalers' stock sales accurately matched that of retail pharmacies and included purchases by panel pharmacies directly from pharmaceutical manufacturers, specialist wholesalers and distribution cooperatives. RESULTS: Mean inhaler retail sales (expressed as percentages of total sales) were 47.5% for pMDIs, 39.5% for DPIs and 13% for nebulisers. The distribution of inhaler sales differed significantly between the countries with pMDI sales greatest in the United Kingdom and Hungary compared to other countries, where DPI sales prevailed. Sales of nebulisation liquids were high in Italy. The pMDI was the most frequently prescribed inhaler for bronchodilators. In contrast, retail sales of DPIs were similar to those of pMDIs for inhaled corticosteroids, and higher in the case of inhalers with combined long-acting ß(2)-agonist and corticosteroid. CONCLUSION: We found a high degree of variability in inhaler prescription between European countries. Differing health policies, costs, health insurance issues, pharmaceutical/commercial aspects and prescribers' and patients' preferences may explain this variation. We suggest a need for more uniform, outcome-led inhaler prescribing practice across Europe to improve the efficacy and cost effectiveness of the treatment of obstructive airways diseases.

Workshop: tuning the 'cough center'.

The Workshop considered the mechanisms whereby the 'cough center' could be tuned by various afferent inputs. There were particular presentations on the effects of inputs from the nose, mouth, respiratory tract and lungs, cerebral cortex, somatic tissues and the pharynx. From all these sites cough induced from the lungs could be increased or decreased in its strength or modified in its pattern. Thus 'tuning' of cough could be due to the interaction of afferent inputs, or to the sensitization or desensitization of brainstem neural pathways. The pattern of response depended on the 'type' of cough being studied and, in some instances, on the timing of the sensory input into the brainstem. Cough inputs could also affect various 'non-cough' motor outputs from the brain, although this was not the main theme of the Workshop. The main conclusion was that cough is not a stereotyped output from the medullary 'cough center', but that its pattern and strength depend on many afferent inputs acting on the 'cough center'.

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

Coughing in laryngectomized patients.

Ablation of the larynx implies withdrawal of afferent information from receptors involved both in the control of expiratory flow and in the genesis of protective airway reflexes including coughing. To investigate the effects of laryngectomy on the sensory and motor component of coughing, maximal voluntary cough (MVC) efforts as well as the reflex cough (RC) responses at threshold (T) and suprathreshold (1.8 x T, ST) levels induced by inhalation of progressively increasing concentrations of ultrasonically nebulized distilled water (fog) were analyzed in 10 laryngectomized patients and 10 control subjects. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGP) and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity (IEMGP/TEC). Cough peak flow was also recorded. Cough threshold was similar in patients and controls, as were IEMGP, TEC, and IEMGP/ TEC recorded during MVC and RCST. In contrast, during RCT, patients' IEMGP was significantly reduced (p < 0.05), thus leading to a significant decrease in IEMGP/TEC (p < 0.05) even in the absence of significant differences in TEC. Cough flow closely correlated with IEMG-related variables. Cough volume acceleration, i. e., the ratio of cough peak flow to the corresponding time to cough peak flow was also significantly reduced in the patients, especially during RCT (p < 0.01). The results suggest that the lack of signals arising from the larynx may result in a reduction of cough volume acceleration as well as in the intensity of abdominal muscle contractions during RCT. These factors may contribute to facilitate the onset and/or the persistence of chest infections in laryngectomized patients.

Repeatability of cough-related variables during fog challenges at threshold and suprathreshold stimulus intensity in humans.

Cough-related variables such as cough frequency, time to onset (i.e. the time until the first cough occurs) and the cough index (i.e. the ratio between the cough frequency and the time to onset) may be important when interpreting results of cough challenges for therapeutic interventions or for comparative research purposes. Nevertheless, repeatability (or reproducibility) for these widely used variables has been poorly studied. In thirty normal subjects, coughing was induced by inhalation of threshold (T) and suprathreshold (1.6 x T) concentrations of ultrasonically nebulized distilled water (fog). Cough threshold was taken as the lowest fog concentration that evoked at least one cough effort during two challenges separated by a 30-min interval. During challenges performed at both threshold and suprathreshold stimulus intensity, cough frequency, time to onset, and the cough index were assessed; within-subject repeatability for these variables was subsequently evaluated. Median +/- interquartile range cough threshold value was 0.9+/-0.5 mL x min(-1). During the two challenges performed to assess cough threshold, the mean +/-SD values of cough frequency, time to onset, and cough index were similar (5.0+/-2.7 and 5.3+/-3.1 coughs x min(-1), 32.4+/-13.3 and 32.9+/-13.6 s, and 0.2+/-0.2 and 0.2+/-0.2, respectively). However, none of these cough-related variables proved to be sufficiently repeatable. During the two challenges performed at suprathreshold stimulus intensity, mean values of cough frequency, time to onset, and cough index were also similar (20.0+/-9.0 and 18.2+/-10.2 coughs x min(-1), 13.5+/-5.8 and 12.0+/-4.62 s, and 1.7+/-1.0 and 1.8+/-1.2); furthermore, all considered variable of suprathreshold challenge turned out to be reproducible. In conclusion, during fog challenges at threshold stimulus intensity, cough frequency, time to onset and cough index cannot reliably be used for evaluating cough responses. However, these cough-related variables may represent useful and reliable research tools in the evaluation of suprathreshold cough responses.

Large and small airway responses to procaterol hydrochloride administered through different extension devices in asthmatic patients.

The effects of spacer devices on the magnitude and velocity of large and small airway bronchodilator responses in asthmatic patients who can correctly operate a metered dose inhaler (MDI) remain unclear. According to a double-blinded, randomized, crossover protocol, 14 asthmatic patients were studied on seven separate occasions. On each occasion, patients inhaled doubling methacholine concentrations until forced expiratory volume in 1 second (FEV1) had fallen by 20% of baseline. Changes in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) were also evaluated. Subsequently, patients were administered 20 or 50 micrograms of procaterol from an MDI either alone or in conjunction with a small- or large-volume spacer device. Changes in FEV1 and FEF25-75 corrected for baseline forced vital capacity (isoFEF25-75) were assessed at 3-minute intervals for 15 minutes and at 30 minutes. Spontaneous recovery was similarly evaluated. The time required to attain significant increases in both FEV1 and isoFEF25-75 was calculated in bronchodilator trials. With 20 micrograms of procaterol, both spacers allowed larger and faster FEV1 increases than the MDI alone (P < 0.01); with 50 micrograms, the velocity and magnitude of FEV1 increases were further enhanced in trials with the MDI alone. The lower procaterol dose via the large-volume spacer determined larger and faster isoFEF25-75 increases than the higher dose via both the small-volume spacer and the MDI alone (P < 0.01). Spacers enhance bronchodilation even in patients using MDIs optimally. Compared with both the small-volume device and the MDI alone, the large-volume spacer allows faster and larger small airway dilation with less than half of the procaterol dose.

Defective motor control of coughing in Parkinson's disease.

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.

A noninvasive electromyographic study on threshold and intensity of cough in humans.

The assessment of cough threshold and intensity is important in respiratory medicine. We have developed a method for objectively and noninvasively assessing cough threshold and intensity of expiratory muscle efforts in response to inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two challenges performed at a 30 min interval. At threshold level, repeatability of peak and slope of the integrated electromyographic (IEMG) activity of abdominal muscles was evaluated. Short- and long-term repeatability of cough threshold were evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively. Dose-response relationships between nebulizer outputs and IEMG-related variables were also investigated, as were the correlations between the latter and expiratory flow during voluntary coughing. The median (1st and 3rd quartile) cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level, peak and slope of IEMG activity were highly reproducible. Cough threshold displayed a high degree of short- and long-term repeatability. Peak and slope of IEMG activity displayed a clear trend to increase (p<0.01) following inhalation of progressively higher UNDW outputs. Maximum flow during voluntary coughs of varying intensity correlated with the peak (p<0.05) and, more closely, with the slope (p<0.01) of abdominal IEMG activity. The assessment of cough threshold as well as the evaluation of the intensity of cough efforts by abdominal integrated electromyographic recordings may represent useful and reliable tools for cough research in humans.

Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip.

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.

Comparison of dose-response slopes obtained by simultaneous assessment of changes in FEV1 and transcutaneous oxygen partial pressure during methacholine challenges in asthmatic patients.

We aimed to ascertain whether monitoring changes in transcutaneous (tc) oxygen partial pressure (PO2) may be used to determine the slope of the dose-response curves to inhaled methacholine. In 10 adult asthmatic patients, FEV1 and tcPO2 were simultaneously measured during inhalation of doubling methacholine concentrations. In each patient, the slopes of the methacholine dose-response curves for FEV1 and tcPO2 were similar and strongly correlated (r = 0.72; p < 0.05). The results indicate that tcPO2 monitoring represents a useful, reliable tool for analysis of the slope of dose-response curves to inhaled methacholine in asthmatic patients. It can also be used to investigate the pathophysiological implications of bronchial hyperreactivity.