Prescribing Patterns for Long-Acting Inhaled Bronchodilators Among Rural Adults With Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is prevalent in rural areas of the USA. Long-acting inhaled bronchodilators (LABDs) are a key tool in COPD management and are underutilized. The purpose of this study was to determine whether rates of prescriptions for LABD differed by payer among patients with COPD in a rural healthcare network. Methods: In analysis 1, a random sample of patients with spirometry- and symptom-confirmed COPD over April 1, 2017 to December 31, 2019 was identified. Patient characteristics, including payer status, extracted from medical records were compared for those who did and did not have any prescriptions for LABD during the study window. In analysis 2, patients with one or more COPD-related hospitalizations during the same time period were identified and similar comparisons were made by LABD prescription status. Results: Among a random sample of patients with spirometry-confirmed COPD, 93.0% had been prescribed LABD during the study window with no difference in proportion by payer. Among the 461 patients with a COPD-related hospitalization, 388 (84.2%) had been prescribed LABD, again with no difference in prescriptions by payer. Those with a COPD-related hospitalization who had been prescribed LABD were younger, had lower body mass index, were more likely to be current smokers and had higher rates of hospitalizations for COPD during the study period than those not prescribed LABD. Conclusion: While disparities in LABD utilization may occur due to cost or other barriers to filling prescriptions, in our study, prescriptions for LABD were common and did not differ by payer status.

A Case of Concomitant COVID-19 Infection-Induced Acute Respiratory Distress Syndrome and Diabetic Ketoacidosis: Another Challenge in Fluid Management.

Coronavirus disease 2019 (COVID-19) has been announced as a pandemic worldwide. The respiratory tract is a target organ system, where infection can result in serious complications, like acute respiratory distress syndrome (ARDS). Management of this condition is more challenging in individuals with diabetes who developed diabetic ketoacidosis. We report a case of a 59-year-old male with type 2 diabetes who presented with productive cough, chills, and shortness of breath for four days. On examination, the patient was hypoxemic with bilateral crackles on lung auscultation. The patient's biochemistry was significant for glucose 387 mg/dL, pH 7.25, positive urine ketones, and lactic acid dehydrogenase (LDH) 325 U/L. An initial chest x-ray showed bilateral peripheral pulmonary infiltrates. The patient was subsequently intubated on the first day for worsening hypoxia due to severe ARDS. He was concomitantly treated for diabetic ketoacidosis (DKA) and hypotension with fluid resuscitation and intravenous insulin. On the same day, his hypoxia worsened with an increase in pulmonary infiltrates, so we stopped intravenous fluids and initiated norepinephrine for 24 hours. His intravenous insulin was initially started at 12 units/hour with subsequent titration down to an average of 5 units/hour. His mechanical ventilation settings followed ARDS guidelines with tidal volume 6 ml/kg based on ideal body weight. Positive COVID-19 was detected from real-time reverse transcription polymerase chain reaction (RT-PCR). After maintaining a negative fluid balance, we were able to extubate in 72 hours. DKA was resolved in 46 hours. In conclusion, type 2 diabetes is rarely affected by DKA, but can be found in up to 27% of cases. There are reports of ARDS as a serious complication in severe DKA in adults and children, yet no data for concomitant DKA and ARDS has been published. We propose that DKA management in COVID-19 patients with ARDS may be similar to the paradigm utilized for other volume restriction in patients with congestive heart failure and end-stage renal failure.

Clinical characteristics of takotsubo cardiomyopathy in north america.

BACKGROUND: Takotsubo cardiomyopathy (TC) or transient left ventricular apical ballooning syndrome is an acute cardiac syndrome characterized by transient wall motion abnormalities extending beyond a single epicardial vessel in the absence of significant obstructive coronary artery disease. AIM: This study was to describe the clinical characteristics of TC in North America. MATERIALS AND METHODS: We identified 10 patients who met the Mayo Clinic criteria for TC using our Electronic Medical Records. We also conducted a systematic review of case series of TC that were done in North America by searching the MEDLINE database. We identified 11 case series that met our eligibility criteria. RESULTS: Our systematic review included 620 patients. Chest pain and ST segment elevation were the cardinal features of this syndrome, but the prevalence was lower than in the European and Asian cohort (50% and 39% as compared with 80% and 70%, respectively). Classic precipitating emotional or physical stress was described in > 80% of patients. Cardiac biomarkers were found to be elevated in >90% of our patients. CONCLUSIONS: TC is a worldwide problem and clinical presentation appears to be similar in North American, European, and Asian countries. However, fewer patients in our cohort presented with typical chest pain and electrocardiography (ECG) changes, which might suggest ethnic variations in the syndrome or perhaps a more aggressive diagnostic approach in North American countries.

The Temporal Evolution of Airways Hyperresponsiveness and Inflammation.

Airways hyperresponsiveness (AHR) is usually produced within days of first antigen exposure in mouse models of asthma. Furthermore, continual antigen challenge eventually results in the resolution of the AHR phenotype. Human asthma also waxes and wanes with time, suggesting that studying the time course of AHR in the allergic mouse would offer insights into the variation in symptoms seen in asthmatics. Mice were sensitized with ovalbumin (OVA) on days 0 and 14. As assessed by airway resistance (Rn ), lung elastance (H) and tissue damping (G), AHR was measured post an OVA inhalation on day 21 (Short Challenge group), after three days of OVA inhalation on day 25 (Standard Challenge group) and following an OVA inhalation on day 55 in mice previously challenged on days 21-23 (Recall Challenge group). Bronchoalveolar lavage was analyzed for inflammatory cells, cytokines and protein. AHR in the Short Challenge group was characterized by an increase in Rn and neutrophil accumulation in the lavage. AHR in the Standard Challenge group was characterized by increases in H and G but by only a modest response in Rn , while inflammation was eosinophilic. In the Standard Challenge protocol, mice lacking fibrinogen were no different from control in their AHR response. AHR in the Recall Challenge group was characterized by increases only in G and H and elevated numbers of both neutrophils and eosinophils. Lavage cytokines were only elevated in the Recall Challenge group. Lavage protein was significantly elevated in all groups. The phenotype in allergically inflamed mice evolves distinctly over time, both in terms of the nature of the inflammation and the location of the AHR response. The study of mouse models of AHR might be better served by focusing on this variation rather than simply on a single time point at which AHR is maximal.

Asthma treatment through the beta receptor: lessons from animal models.

Asthma is a significant health problem worldwide with a prevalence that continues to rise and for which there is no cure. Animal models have been used for decades to investigate the cause and cures of asthma, and while they do not always mimic many of the facets of this syndrome, mechanistic animal studies are still nevertheless very useful. Animal studies with beta-agonists suggest much broader and perhaps more important roles for beta-agonists since beta-agonists reduce aspects of inflammation and may affect structural remodeling. Studies using enantiomers of beta-agonists provide a confusing picture of the degree and mechanism of the deleterious effects of racemic mixtures and/or the S-enantiomer or other classes of beta-agonists. Neural mechanisms are implicated. The future holds a promise of even more insight into the mechanisms of the acute and chronic role of the beta-adrenoceptor, asthma therapeutics, in particular, beta-agonists that will lead to a better understanding of the pathogenesis and treatment of asthma.

Detrimental effects of albuterol on airway responsiveness requires airway inflammation and is independent of ß-receptor affinity in murine models of asthma.

BACKGROUND: Inhaled short acting ß2-agonists (SABA), e.g. albuterol, are used for quick reversal of bronchoconstriction in asthmatics. While SABA are not recommended for maintenance therapy, it is not uncommon to find patients who frequently use SABA over a long period of time and there is a suspicion that long term exposure to SABA could be detrimental to lung function. To test this hypothesis we studied the effect of long-term inhaled albuterol stereoisomers on immediate allergic response (IAR) and airway hyperresponsiveness (AHR) in mouse models of asthma. METHODS: Balb/C mice were sensitized and challenged with ovalbumin (OVA) and then we studied the IAR to inhaled allergen and the AHR to inhaled methacholine. The mice were pretreated with nebulizations of either racemic (RS)-albuterol or the single isomers (S)- and (R)-albuterol twice daily over 7 days prior to harvest. RESULTS: We found that all forms of albuterol produced a significant increase of IAR measured as respiratory elastance. Similarly, we found that AHR was elevated by albuterol. At the same time a mouse strain that is intrinsically hyperresponsive (A/J mouse) was not affected by the albuterol isomers nor was AHR induced by epithelial disruption with Poly-L-lysine affected by albuterol. CONCLUSIONS: We conclude that long term inhalation treatment with either isomer of albuterol is capable of precipitating IAR and AHR in allergically inflamed airways but not in intrinsically hyperresponsive mice or immunologically naïve mice. Because (S)-albuterol, which lacks affinity for the ß2-receptor, did not differ from (R)-albuterol, we speculate that isomer-independent properties of the albuterol molecule, other than ß2-agonism, are responsible for the effect on AHR.

Inhaled salmeterol and/or fluticasone alters structure/function in a murine model of allergic airways disease.

BACKGROUND: The relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting beta-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT. RESULTS AND DISCUSSION: Treatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol. CONCLUSIONS: Fluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.

It's not all smooth muscle: non-smooth-muscle elements in control of resistance to airflow.

To achieve gas exchange, inspired air must pass through an intricate and dynamic tracheobronchial tree. The tree offers resistance to airflow, and increased resistance is the most important functional change in lung disease. Numerous mechanisms contribute to increased resistance by causing airway narrowing, closure, occlusion, and/or obliteration. Although airway smooth muscle (ASM) contraction and shortening are an important cause of increased resistance, non-ASM elements can also contribute. Nonmuscle elements can modify the amount of airway narrowing for any given level of ASM shortening and the amount of shortening for a given level of ASM activation. In this review, we outline the physiological basis for airflow resistance and describe how changes in the lung parenchyma, the airways, and their luminal contents can contribute to increased airflow resistance. A detailed understanding of the mechanisms and consequences of increased airway resistance is vital to our attempts to alleviate the enormous burden of suffering caused by obstructive lung diseases.

Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17.

Dysfunctional expression of T-bet, a transcription factor that is critical for IFN-gamma production, has been implicated in the development of asthma. To investigate in detail the mechanisms responsible for exacerbated disease in the absence of T-bet expression, BALB/c wild-type (WT) and T-bet(-/-) mice were used in a murine model of OVA-induced allergic lung inflammation. Following OVA challenge, T-bet(-/-) mice displayed increased histological inflammation in the lungs as well as greater thickening of the bronchiole linings, increased numbers of eosinophils and neutrophils in the lung, and enhanced airway hyperresponsiveness, compared with WT mice. However, the production of Th2 cytokines in T-bet(-/-) mice did not appear to be significantly greater than in WT mice. Interestingly, a marked increase in the levels of the proinflammatory cytokine IL-17 was observed in T-bet(-/-) mice. Neutralization of pulmonary IL-17 in T-bet(-/-) mice by anti-IL-17 mAb treatment during OVA challenge resulted in decreased levels of neutrophilic infiltration into the airways and decreased airway inflammation, essentially reversing the development of allergic asthma development. These findings indicate that IL-17 is a key mediator of airway inflammation in the absence of T-bet. The results of this study suggest a possible target for therapeutic intervention of human asthma.

Radon awareness and mitigation in Vermont: a public health survey.

Radon exposure is associated with an increased incidence of lung cancer, and elevated levels may be found in as many as 1 out of 15 homes. The U.S. EPA recommends testing homes for radon and mitigating over the advisory level of 4 picocuries per liter (4 pCi L(-1), or 148 Bq m(-3)). A sample population from a list of Vermont residents who had tested their residence for radon through the Vermont Department of Health and who had elevated levels were mailed a survey to assess demographic characteristics, knowledge about radon, mitigation rates, types of mitigation, as well as barriers to mitigation. The response rate was 63%. Forty-three percent of respondents mitigated. Roughly half were not completely knowledgeable of radon based upon the ability to associate radon exposure with lung cancer risk. Reasons not to mitigate radon levels in homes were cost and lack of concern over elevated levels. A multivariate logistic regression analysis revealed factors associated with mitigating: an education level of college or higher (p = 0.02), concern that a high radon level would affect real estate value (p = 0.04), and home age less than 10 y (p = 0.05). In summary, less than half of Vermonters with elevated radon levels participating in the Department of Health program mitigated. We identify factors associated with radon mitigation that may lead to improved radon education and mitigation practice.