Exacerbation Of Obstructive Airways Disease Research Articles

Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia.

Vitamin D deficiency is a risk factor for exacerbation of obstructive airway disease, a hallmark of which is mucus dehydration and plugging. Calcitriol (the active form of vitamin D) deficiency in cultured human airway epithelia resulted in increased SCNN1G and ATP1B1 mRNAs encoding subunits of ENaC and the Na-K pump compared with supplemented epithelia. These drive the absorption of airway surface liquid. Consistently, calcitriol-deficient epithelia absorbed liquid faster than supplemented epithelia. Calcitriol deficiency also increased amiloride-sensitive Isc and Gt without altering Na-K pump activity, indicating the changes in amiloride-sensitivity arose from ENaC. ENaC activity can be regulated by trafficking, proteases, and channel abundance. We found the effect was likely not induced by changes to endocytosis of ENaC given that calcitriol did not affect the half-lives of amiloride-sensitive Isc and Gt. Furthermore, trypsin nominally increased Isc produced by epithelia ± calcitriol, suggesting calcitriol did not affect proteolytic activation of ENaC. Consistent with mRNA and functional data, calcitriol deficiency resulted in increased γENaC protein. These data indicate that the vitamin D receptor response controls ENaC function and subsequent liquid absorption, providing insight into the relationship between vitamin D deficiency and respiratory disease.NEW & NOTEWORTHY It is unknown why calcitriol (active vitamin D) deficiency worsens pulmonary disease outcomes. Results from mRNA, immunoblot, Ussing chamber, and absorption experiments indicate that calcitriol deficiency increases ENaC activity in human airway epithelia, decreasing apical hydration. Given that epithelial hydration is required for mucociliary transport and airway innate immune function, the increased ENaC activity observed in calcitriol-deficient epithelia may contribute to respiratory pathology observed in vitamin D deficiency.

Study of Prevalence and Pattern of Infections in Acute Exacerbations of Obstructive Airway Disease

Objective: To study the prevalence and pattern of infections causing exacerbations of obstructive airway diseases.
 Methods: A prospective cross sectional study which included 126 consecutive obstructive airway disease patients were enrolled for the study. All the included patients were subjected to detailed history, clinical examination and routine investigations including sputum Gram’s stain and aerobic culture after obtaining a written informed consent. Pharyngeal swab was collected and sent in Viral Transport Medium(VTM, Himedia) within 24hrs to Regional Medical Research Centre (ICMR),Bhubaneswar for detection of respiratory viruses. Samples were tested by Real Time reverse-transcription polymerase chain reaction (RT-PCR).
 Results: Among patients with COPD, Flu A/H3N2(9.375%) was found in highest number of patients followed by rhinovirus(7.3%). In bronchial asthma patients,virus was isolated only in 3 cases(13.6%).No virus was detected in bronchiectasis patients. Isolated bacterial infection was detected in 26 cases (20.63%).Acinetobacter baumanii and Klesiella pneumoniae were most common bacterial pathogens detected.Bacterial pathogens were commonly isolated among COPD patients.Co-infection with both bacteria and virus was detected in 12 patients (9.52%)of which 11 were diagnosed with COPD. Only 1 case of bronchial asthma reported a co-infection.Among cases with co-infection with both bacteria and virus,Acinetobacter baumanii and Pseudomonas aeruginosa were found to be most common bacterial pathogens.There was no typical pattern in viral infection among the cases throughout the year.
 Conclusion: The risk of exacerbation due to viral etiology is perennial but might be self limiting. Recovery from exacerbation takes a long time and patients with exacerbations have an impaired quality of life, diminished exercise capacity and loss of lung function.

A Clinical Study on Risk Factors and Appropriateness of Antibiotic Prescribing For Infective Exacerbation of Obstructive Airway Disease in Old Aged Patients

Medication Appropriate Index (MAI) is used to assess the quality of antibiotic prescribing. The aim of the study to determine the risk factors of obstructive airway disease and to assess the appropriateness of ongoing antibiotic therapy using medication appropriate index criteria. A 6 months study was carried out at Karuna Medical College Chittur. The patient details were collected in a specially designed data entry form and results were statistically analysed using chi square test. During the study period, a total of 202 patients were enrolled. Out of this, 150 (74%) were male patients and 52 (26%) were female patients and Distribution of risk factors, ex-smokers 34 (15%) were more prone to infective exacerbations, followed by smokers 34 (17%), alcoholics 33 (16%), allergies 12 (6%), ex-alcoholics 8 (4%) and patients with both smoking and alcoholism were 10 (5%). The most common problems were seen with indication (68%), duration of therapy (74%), and dose of antibiotic (81%), directions (68%), duplication (64%), effectiveness (75%) and expensiveness (68%). The level of significance was assessed and found to be significant. Males are more affected than females. The cigarette smoking influences the rate of influence of lung function by causing path physiologic changes in airways, including inflammation hyper responsiveness. Using medication appropriate index criteria when comparing inappropriate v/s marginal and inappropriate v/s appropriate both shows high level of significance which imply antibiotic therapy was inappropriate. It is found that inappropriate use of antibiotics will increase the burden of multi-drug resistance. Prescribing under generic name is considered economical and rational

Effect of Structured Physical Activity on Respiratory Outcomes in Sedentary Elderly Adults with Mobility Limitations.

To evaluate the effect of structured physical activity on respiratory outcomes in community-dwelling elderly adults with mobility limitations. Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over an intervention period of 24-42months. Physical activity included walking (goal of 150min/week) and strength, flexibility, and balance training. Health education included workshops on topics relevant to older adults and upper extremity stretching exercises. Lifestyle Interventions and Independence in Elders (LIFE) Study. Community-dwelling persons aged 70-89 with Short Physical Performance Battery scores less than 10 (N=1,635). Dyspnea severity (defined as moderate to severe according to a Borg index >2 immediately after a 400-m walk), forced expiratory volume in 1second (FEV1) (<lower limit of normal (LLN) defined low breathing capacity), and maximal inspiratory pressure (MIP) (<LLN defined respiratory muscle weakness) were assessed at baseline and 6, 18, and 30months. Hospitalization for exacerbation of obstructive airways disease (EOAD) and pneumonia was also ascertained over the 42-month follow-up period. The randomized groups were similar in baseline demographics, including mean age (79) and sex (67% female). The effect of physical activity on dyspnea severity, FEV1, and MIP was no different from that of health education but was associated with higher likelihood of respiratory hospitalization, significantly for EOAD (hazard ratio (HR)=2.34, 95% confidence interval (CI)=1.19-4.61, P=.01) and marginally for pneumonia (HR=1.54, 95% CI=0.98-2.42, P=.06). In older persons with mobility limitations, physical activity was associated with higher likelihood of respiratory hospitalization than health education, but differences in dyspnea severity, FEV1, and MIP did not accompany this effect-indicating that higher hospital use could be attributable to greater participant contact.

Pneumocystis Infection in an Immunocompetent Host Can Promote Collateral Sensitization to Respiratory Antigens

Infection with the opportunistic fungal pathogen Pneumocystis is assumed to pass without persistent pathology in immunocompetent hosts. However, when immunocompetent BALB/c mice were inoculated with Pneumocystis, a vigorous Th2-like pulmonary inflammation ensued and peaked at 14 days postinfection. This coincided with a 10-fold increase in the number of antigen-presenting cells (APCs) in the lung, and these cells were capable of presenting antigen in vitro, as well as greater uptake of antigen in vivo. When mice were presented with exogenous antigen at the 14-day time point of the infection, they developed respiratory sensitization to that antigen, in the form of increased airway hyperresponsiveness upon a later challenge, whereas mice not infected but presented with antigen did not. Like other forms of collateral sensitization, this response was dependent on interleukin-4 receptor signaling. This ability to facilitate sensitization to exogenous antigen has been previously reported for other infectious disease agents; however, Pneumocystis appears to be uniquely capable in this respect, as a single intranasal dose without added adjuvant, when it was administered at the appropriate time, was sufficient to initiate sensitization. Pneumocystis infection probably occurs in most humans during the first few years of life, and in the vast majority of cases, it fails to cause any overt direct pathology. However, as we show here, Pneumocystis can be an agent of comorbidity at this time by facilitating respiratory sensitization that may relate to the later development or exacerbation of obstructive airway disease.

Hyperinflation-induced cardiorespiratory failure in rats

We previously showed that severe inspiratory resistive loads cause acute (<1 h) cardiorespiratory failure characterized by arterial hypotension, multifocal myocardial infarcts, and diaphragmatic fatigue. The mechanisms responsible for cardiovascular failure are unknown, but one factor may be the increased ventricular afterload caused by the large negative intrathoracic pressures generated when breathing against an inspiratory load. Because expiratory threshold loads increase intrathoracic pressure and decrease left ventricular afterload, we hypothesized that anesthetized rats forced to breathe against such a load would experience only diaphragmatic failure. Loading approximately doubled end-expiratory lung volume, halved respiratory frequency, and caused arterial hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive. Although hyperinflation immediately reduced the diaphragm's mechanical advantage, fatigue did not occur until near load termination. Mean arterial pressure progressively fell, becoming significant (cardiovascular failure) midway through loading despite tachycardia. Loading was terminated (endurance 125 +/- 43 min; range 82-206 min) when mean arterial pressure dropped below 50 mmHg. Blood samples taken immediately after load termination revealed hypoglycemia, hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that was, according to histology, mainly in the right ventricle. This damage probably reflects a combination of decreased O(2) delivery (decreased venous return and arterial hypoxemia) and greater afterload due to hyperinflation-induced increase in pulmonary vascular resistance. Thus, in rats breathing at an increased end-expiratory lung volume, cardiorespiratory, not just respiratory, failure still occurred. Right heart injury and dysfunction may contribute to the increased morbidity and mortality associated with acute exacerbations of obstructive airway disease.

A new measure of acute physiological derangement for patients with exacerbations of obstructive airways disease: The COPD and Asthma Physiology Score

Decisions about how to treat patients with acute exacerbations of obstructive airways disease-chronic obstructive pulmonary disease (COPD), asthma or mixed diagnoses-often require an understanding of prognosis. This depends on the severity of the acute deterioration and the patient's functional reserve. There are currently no validated disease-specific scores that measure the severity of the acute exacerbation. To develop an acute physiology score for exacerbations of obstructive airways disease. Secondary analysis of a high-quality clinical database, the Case Mix Programme Database. One hundred and sixty-eight adult, general critical care units in England, Wales and Northern Ireland. A total of 8527 patients with obstructive airways disease were identified with a mean (SD) age of 65.9 (9.7) years and hospital mortality of 35.5%. The COPD and Asthma Physiology Score (CAPS) was developed using logistic regression. The CAPS included eight variables: heart rate, mean arterial blood pressure, pH, sodium, urea, creatinine, albumin and white blood cell count. The score had fair discrimination with an area under the receiver operating characteristic curve of 0.718. This performance was reproduced in a further validation dataset of 7957 patients. The discrimination of the CAPS in these validation data exceeded that of the acute physiology scores from APACHE II and III and the physiological components of SAPS II. The CAPS can be used to estimate the prognostic impact of physiological derangements accompanying an acute exacerbation of obstructive airways disease and has the potential for even greater predictive performance when combined with measures of a patient's functional reserve.

Diagnosis of Streptococcus pneumoniae pneumonia by quantitative enzyme linked immunosorbent assay of C-polysaccharide antigen.

To evaluate the use of a quantitative enzyme linked immunosorbent assay (ELISA) detecting C-polysaccharide (PnC) antigen in sputum for the diagnosis of Streptococcus pneumoniae infection. Specimens of sputum from 60 patients with acute community and hospital acquired pneumonia and infective exacerbations of obstructive airways disease were examined by semiquantitative culture and antigen ELISA. Using a cutoff value of 1 microgram/ml PnC antigen for a positive result, the sensitivity of this assay was 90.3%, specificity 93.1%, predictive value of a positive result was 93.5%, and the predictive value of a negative result 89.6%. Quantitation of C-polysaccharide antigen in sputum by ELISA distinguishes between carriage of oral bacteria which express PnC-like antigen and infection with S pneumoniae and compares favourably with other diagnostic methods.

Guidelines for the selective ordering of admission chest radiography in adult obstructive airway disease.

To validate previously developed guidelines for the selective use of chest radiography in adults admitted for exacerbation of obstructive airway disease. Prospective, observational cohort study using criteria developed in a previous retrospective study. Unselected convenience sample of 128 adults with obstructive airway disease who did not respond to standard emergency department treatment and required admission. Municipal hospital ED and inpatient medical service. Patients were categorized as "complicated" or "uncomplicated" according to previously developed criteria. Management was recorded as altered if the patient's physician answered the question, "Did the chest radiography alter your management of this patient?" affirmatively. Of 27 patients whose management was altered by the chest radiography, 26 were classified as complicated, for a sensitivity of 96% (95% confidence interval [CI], 81, 100). One of 44 admissions classified as uncomplicated had management altered by the chest radiography (negative predictive value, 98%, 95% CI, 88, 100). This chest radiography was later reread as normal. Classification as an uncomplicated patient with obstructive airway disease was strongly associated with either a normal chest radiography or a radiographic finding that was clinically unimportant (P = .0002). Patients with acute exacerbation of obstructive airway disease who are otherwise uncomplicated do not benefit from routine admission chest radiography. The use of this simple clinical strategy would safely reduce the number of chest radiographs by about one-third in this and similar patient populations, decreasing both health care costs and exposure to ionizing radiation.

The safety of oxygen‐driven nebulisers in patients with chronic hypoxaemia and hypercapnia

ABSTRACTThere is potential to cause deterioration due to hypoxia in patients with acute exacerbation of obstructive airways disease with the indiscriminate use of aerosol bronchodilators delivered by air‐driven nebulisers without supplemental oxygen. Traditionally, air‐driven nebulisers have been reserved for the treatment of chronically hypoxic and hypercapnic patients with an exacerbation of chronic obstructive pulmonary disease (COPD). The purpose of this pilot study was to assess the safety of oxygen‐driven nebulisers (6 L/min) in the treatment of COPD patients.Sixteen patients received bronchodilator via an oxygen‐driven nebuliser for 30 minutes. No patient deteriorated clinically and in all the PaO2 rose significantly (mean baseline 43.7 ± 6.3 mmHg (± SD) post nebuliser 108.8 ± 30.4 mmHg). There was an insignificant rise in PaC02 from 59.7 ± 9.1 mmHg to 66.4 ± 15.3 mmHg and this was not important clinically.On the basis of this pilot study, we suggest that aerosol bronchodilators may be safely delivered by oxygen‐driven nebulisers in chronically hypoxic and hypercapnic COPD patients. A larger scale formal trial is indicated to compare oxygen‐driven versus air‐driven nebulisers in COPD.

Prolonged Neurogenic Weakness in Patients Requiring Mechanical Ventilation for Acute Airflow Limitation

We describe three patients who required mechanical ventilation for severe acute exacerbations of obstructive airways disease. When treatment with sedatives and muscle relaxants was withdrawn, they exhibited profound generalized weakness and consequently required prolonged ventilation despite resolution of the airway obstruction. Clinical features were variable, but none of the patients developed failure of other organs and infection was confined to the lungs. All had electrophysiologic evidence of a predominantly motor axonal syndrome. One patient in whom sensory action potentials were abnormal may represent an unusually severe case of critical illness neuropathy occurring in the absence of systemic sepsis and multiple organ failure. In the other two cases, this diagnosis is made less likely by the complete absence of sensory involvement and in these patients the lesion appeared to be either in the most distal portion of the motor neuron or at the neuromuscular junction. In all three patients, resolution was slow but eventually complete. The etiology of the condition is not clear, but it seems to be distinct from the acute myopathy previously described in asthmatics who had received mechanical ventilation. It is important to recognize this phenomenon to avoid erroneous conclusions about the likelihood of the patient recovering from ventilator dependence. A prolonged weaning period is to be expected in such cases.

Aerosol Bronchodilator Delivery Methods

• Thirty-six acutely ill, hospitalized patients with acute exacerbations of obstructive airway disease and a greater than 10% increase in forced expiratory volume in 1 s after administration of aerosolized bronchodilator were randomized to receive either metaproterenol sulfate delivered by updraft-compressor nebulization (UDN) or terbutaline sulfate delivered by metered-dose inhaler (MDI) with a spacer. Serial analyses of pulmonary function measurements were performed with the use of 95% confidence intervals for the percentage response ratios of MDI to UDN. The response to MDI was at least equivalent to that of UDN, and MDI use was associated with no prolongation of hospital stay. Equivalent bronchodilation was achieved with MDI therapy with a lower daily charge for therapy for each patient and less respiratory therapist time. In hospitalized bronchodilator-responsive patients with acute exacerbations of obstructive airway disease, the MDI/spacer combination is the preferred approach when the status of the patient allows its use. (<i>Arch Intern Med</i>1989;149:618-623)

How Safe are β-Blockers?

The benefit/risk ratio of β- blocking drugs is reviewed in the light of many years of widespread use. It is reasonably certain that the ‘practolol syndrome’ will not occur in association with the currently available and commonly prescribed β- blockers. Other predictable side effects, such as bradycardia, fatigue and cold peripheries are discussed, as well as the possibility of exacerbation of obstructive airways disease, heart failure and intermittent claudication while on β- blocking drugs. The incidence of these and other side effects is discussed in relation to the pharmaco- kinetic properties of various β- blockers and it is concluded that all β- blockers have a high benefit/risk ratio and that the ideal β- blocker profile for optimal safety and acceptability is high cardioselectivity plus high hydrophilicity (low lipid solubility).

Exacerbation of Obstructive Airway Disease by Timolol

<h3>To the Editor.—</h3> Timolol maleate, a widely prescribed drug for treatment of glaucoma, is a nonselective β-adrenergic blocking agent. Its administration in the form of eyedrops to patients with obstructive airways disease may cause bronchoconstriction.¹Hence, it is imperative that those caring for patients with glaucoma, ophthalmologists and primary care physicians alike, appreciate the potentially harmful systemic effects of this valuable drug. We have seen three patients whose obstructive airway disease was aggravated by timolol therapy. <h3>Report of Cases.—Case 1.—</h3> A 68-year-old man with severe emphysema received a single dose of 0.25% timolol maleate eyedrops. Soon thereafter he became severely dyspneic and required hospitalization. On examination he showed signs of severe airway obstruction. After several hours of intensive treatment with aminophylline, terbutaline sulfate, and corticosteroids, his respiratory status returned to normal. He has had no further such attacks in the succeeding six months. <h3>Case 2.—</h3> A 73-year-old

Exacerbation of obstructive airway disease by timolol

Exacerbation of obstructive airway disease by timolol