Krishna M. Sundar

Chronic cough and obstructive sleep apnea in a community-based pulmonary practice

BackgroundRecent reports suggest an association between unexplained chronic cough and obstructive sleep apnea (OSA). Current guidelines provide an empiric integrative approach to the management of chronic cough, particularly for etiologies of gastroesophageal reflux (GERD), upper airway cough syndrome (UACS) and cough variant asthma (CVA) but do not provide any recommendations regarding testing for OSA. This study was done to evaluate the prevalence of OSA in patients referred for chronic cough and examine the impact of treating OSA in resolution of chronic cough.MethodsA retrospective review of chronic cough patients seen over a four-year period in a community-based pulmonary practice was done. Patients with abnormal chest radiographs, abnormal pulmonary function tests, history of known parenchymal lung disease, and inadequate followup were excluded. Clinical data, treatments provided and degree of resolution of cough was evaluated based on chart review. Specifically, diagnostic testing for OSA and impact of management of OSA on chronic cough was assessed.Results75 patients with isolated chronic cough were identified. 44/75 had single etiologies for cough (GERD 37%, UACS 12%, CVA 8%). 31/75 had multiple etiologies for their chronic cough (GERD-UACS 31%, GERD-CVA 5%, UACS-CVA 3%, GERD-UACS-CVA 3%). 31% patients underwent further diagnostic testing to evaluate for UACS, GERD and CVA. Specific testing for OSA was carried out in 38/75 (51%) patients and 33/75 (44%) were found to have obstructive sleep apnea. 93% of the patients that had interventions to optimize their sleep-disordered breathing had improvement in their cough.ConclusionsOSA is a common finding in patients with chronic cough, even when another cause of cough has been identified. CPAP therapy in combination with other specific therapy for cough leads to a reduction in cough severity. Sleep apnea evaluation and therapy needs to considered early during the management of chronic cough and as a part of the diagnostic workup for chronic cough.

Sepsis induced immunosuppression: Implications for secondary infections and complications

Sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis. This review explores the basis for sepsis related immune dysfunction and discusses its clinical implications for the treating intensivist. Recent trends indicate that a significant proportion of septic patients succumb to the complications of secondary infections and chronic critical care illness from the initial bout of sepsis. Therefore care-givers in the ICU need to be aware of the impediments posed by sepsis-related immune dysfunction that can impair recovery in patients with sepsis and contribute to sepsis-related mortality.

Chronic Cough and OSA: A New Association?

Chronic cough is defined as cough lasting more than 2 months. Common causes for chronic cough in nonsmokers with normal chest radiographs and pulmonary functions include gastroesophageal reflux disease (GERD), cough-variant asthma (CVA), and upper airway cough syndrome (UACS). Current guidelines recommend diagnosing the etiology of chronic cough based upon the results of therapy for suspected GERD, CVA, and UACS. Despite following current recommendations for diagnosis and treatment, the cause for a significant proportion of chronic cough remains unexplained.Recent reports indicate the resolution of chronic cough following treatment of concomitantly diagnosed obstructive sleep apnea (OSA). Whether this represents a co-occurrence of two commonly prevalent disorders or a pathophysiologic relationship between OSA and cough remains unknown. This review offers insights into a pathophysiologic link between OSA and the commonly purported etiologies for cough, namely, GERD, UACS, and CVA. In addition, evidence for a relationship between airway inflammation that can trigger or perpetuate cough and OSA is discussed. This review explores mechanisms by which nocturnal continuous positive airway therapy resolves cough by improving underlying airway inflammation secondary to OSA and impacts upon GERD, CVA, and UACS.

Granulomatous pneumonitis following bone marrow transplantation

We describe the rare occurrence of a granulomatous pneumonitis seen in a patient following allogeneic bone marrow transplantation. Interestingly sarcoidosis was diagnosed in the marrow donor less than a year after donating his bone marrow. Bone Marrow Transplantation (2001) 28, 627–630.

A longitudinal study of CPAP therapy for patients with chronic cough and obstructive sleep apnoea

BackgroundChronic cough patients are rendered therapies for gastro-esophageal reflux (GERD), upper airway cough syndrome (UACS) and cough-variant asthma (CVA) with varying benefit. Idiopathic or unexplained cough has emerged as an important clinical entity in both primary care and subspecialty clinics. Recent evidence points to a link between chronic cough and untreated obstructive sleep apnea (OSA).MethodsA prospective observational study was done to evaluate the effect of OSA therapy in patients with chronic cough. Patients enrolled into the study underwent questionnaires to evaluate for GERD, UACS and CVA along with screening questionnaires for OSA and daytime sleepiness. The Leicester cough questionnaire (LCQ) was done at baseline and during serial visits to evaluate cough intensity and was used as the primary outcome measure of the effect of CPAP therapy on chronic cough.ResultsOut of 37 patients enrolled into the study, only 28 patients had follow up LCQ scores available and therefore underwent analysis. 22/28 patients were suspected to have OSA based on abnormal STOP-BANG screening questionnaire scores and overnight oximetry abnormalities. Of these 19/28 patients had overnight attended polysomnography with definitive diagnosis of OSA yielding a 68% prevalence of OSA in our chronic cough population. Chronic cough patients treated for OSA tended to be older with a significantly higher BMI than chronic cough patients without OSA. Significant improvement of LCQ scores occurred with CPAP therapy for OSA in chronic cough patients.ConclusionOSA is significantly prevalent in chronic cough patients. Subjects with chronic cough and OSA tend to be older and obese. Treatment of OSA in chronic cough patients yields significant improvement in their health status.

Severity of cough in idiopathic pulmonary fibrosis is associated with MUC5 B genotype

BackgroundA polymorphism (rs35705950) in the promoter region of the mucin MUC5B is associated with both familial and sporadic forms of idiopathic pulmonary fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the expression of cough, a frequent disabling symptom seen in subjects with IPF.MethodsWe genotyped 136 subjects with IPF. All living subjects were provided with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed allele effects of the MUC5B polymorphism on the LCQ scores using SAS General Linear Models (GLM) in the patients with IPF.ResultsIn the 68 of the total 136 IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent with prior published studies (31%). We found a significant independent effect of the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is independent of other common causes of cough, including gastroesophogeal reflux disease and upper airway cough syndrome.ConclusionsCough severity, a common disabling phenotypic component of IPF, is significantly associated with the presence of the minor allele of a MUC5B promoter polymorphism. This study highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary fibrosis.

Comparison of ventilator-associated pneumonia (VAP) rates between different ICUs: Implications of a zero VAP rate

OBJECTIVE Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality. Measures to reduce the incidence of VAP have resulted in institutions reporting a zero or near-zero VAP rates. The implications of zero VAP rates are unclear. This study was done to compare outcomes between two intensive care units (ICU) with one of them reporting a zero VAP rate. DESIGN, SETTING AND PATIENTS This study retrospectively compared VAP rates between two ICUs: Utah Valley Regional Medical Center (UVRMC) with 25 ICU beds and American Fork Hospital (AFH) with 9 ICU beds. Both facilities are under the same management and attended by a single group of intensivists. Both ICUs have similar nursing and respiratory staffing patterns. Both ICUs use the same intensive care program for reduction of VAP rates. ICU outcomes between AFH (reporting zero VAP rate) and UVRMC (VAP rate of 2.41/1000 ventilator days) were compared for the years 2007-2008. MEASUREMENTS AND MAIN RESULTS UVRMC VAP rates during 2007 and 2008 were 2.31/1000 ventilator days and 2.5/1000 ventilator days respectively compared to a zero VAP rate at AFH. The total days of ventilation, mean days of ventilation per patient and mean duration of ICU stay per patient was higher in the UVRMC group as compared to AFH ICU group. There was no significant difference in mean age and APACHE II score between ICU patients at UVRMC and AFH. There was no statistical difference in rates of VAP and mortality between UVRMC and AFH. CONCLUSIONS During comparisons of VAP rate between institutions, a zero VAP rate needs to be considered in the context of overall ventilator days, mean durations of ventilator stay and ICU mortality.

Clinical Course of ICU Patients With Severe Pandemic 2009 Influenza A (H1N1) Pneumonia Single Center Experience With Proning and Pressure Release Ventilation

Received June 10, 2010, and in revised form July 26, 2010. Accepted for publication August 12, 2010. Background: A number of different modalities have been employed in addition to conventional ventilation to improve oxygenation in patients with severe 2009 pandemic influenza A (H1N1) pneumonia. Outcomes with ventilatory and rescue therapies for H1N1 influenza-related acute respiratory distress syndrome (ARDS) have been varied.1–6 A single intensive care unit (ICU) experience with management of laboratory-confirmed 2009 pandemic influenza A (H1N1) ARDS with a combination of proning and airway pressure release ventilation (APRV) is described. Methods: A retrospective review of medical records of ICU patients seen at Utah Valley Regional Medical Center during the first and second waves of the H1N1 influenza pandemic was done. Results: Fourteen ICU patients were managed with invasive ventilation for 2009 pandemic influenza A (H1N1)-related ARDS. Hypoxemia refractory to conventional ventilation was noted in 11 of 14 patients despite application of APRV. Following proning in patients on APRV, improvement of hypoxemia and hemodynamic status was achieved. Only 2 of 11 patients on APRV and proning required continuous dialysis. Mortality in intubated patients receiving a combination of proning and APRV was 27.3% (3/11) with 2 of these dying during the first wave of the H1N1 influenza pandemic. In all, 3 of 11 patients on proning and APRV underwent tracheostomy, with 2 of these undergoing tube thoracostomy. ARDSnet fluid-conservative protocol was safely tolerated in 8 of 11 of the intubated patients following initiation of proning and APRV. Conclusions: Proning in combination with APRV provides improvement of hypoxemia with limitation of end-organ dysfunction and thereby facilitates recovery from severe 2009 pandemic influenza A (H1N1).

Regulation of erythropoiesis after normoxic return from chronic sustained and intermittent hypoxia

Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF), which regulate erythropoietin transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species in reticulocytes mediated by downregulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes. Decreased CAT results from hypoxia-induced miR-21 that downregulates CAT. This correlates with a transient acute decrease of HIF-1 at normoxic return that is associated with normalization of red cell mass.

Clinical course and spectrum of intensive care unit patients reactivating herpes simplex-1 virus: A retrospective analysis

Background: Herpes simplex-1 virus (HSV-1) reactivation in the respiratory tract is common in intensive care unit (ICU) patients. However, susceptible ICU populations are poorly defined. Clinical recognition of HSV infection of the respiratory tract is difficult and the impact of such reactivation is not understood. Materials and Methods: A retrospective analysis of HSV-1 positive patients encountered over a 5-year period at a multispecialty ICU was carried out. HSV-1 was identified in respiratory secretions using a qualitative polymerase chain reaction (PCR) technique. Patient charts were reviewed for clinical features that would typify HSV-1 respiratory involvement, and the morbidity and mortality risks found with HSV-1 respiratory involvement. Results: A review of 48 HSV-1 positive ICU patients showed that patients reactivating HSV in the respiratory tract fell into one of the three categories: (1) septic elderly patients with and without ARDS, (2) immunosuppressed patients, especially those receiving high-dose steroids, and (3) post-thoracotomy patients. Abnormalities suggestive of HSV-1 reactivation in the respiratory tract included, haemorrhagic or excessive respiratory secretions, concomitant orofacial herpes (42%), and bronchoscopic abnormalities (hemorrhagic ulcers and mucosal friability) (83%). Twenty eight percent of the HSV-1 infected patients experienced postextubation stridor. HSV-1 reactivation was associated with extended ventilator stays, significant mortality (42%), and ventilator-associated pneumonias (52%). Conclusions: Identification of susceptible populations and definition of clinical features of HSV-1 related respiratory disease can enable diagnosis of HSV-1 infection in ICU patients. Although detection by a PCR technique can rapidly diagnose HSV-1 reactivation, prospective studies are required to clarify HSV disease versus mere shedding, and understand the impact of HSV-1 reactivation in hospitalized patients.