The management of life-threatening airflow obstruction

Summary Patients with status asthmaticus commonly develop progressive airflow obstruction over hours to days as a result of airway wall inflammation, bronchospasm and intraluminal mucus. In sudden asphyxic asthma, airflow obstruction results primarily from smooth muscle mediated bronchospasm. Airflow obstruction causes ventilation-perfusion inequality, lung hyperinflation, and increased work of breathing. Severe cases are characterized by an inability to speak, diaphoresis, altered mental status, poor air movement, widened pulsus paradoxus, accessory muscle use, and low peak expiratory flow rate. Lack of early response to bronchodilator therapy, a rising partial pressure of carbon dioxide, and need for assisted ventilation are additional markers of severe disease. First line treatment consists of oxygen, beta agonists, and corticosteroids. In mechanically ventilated patients, bronchodilators must be given in higher dosages to achieve a physiologic effect. Agents of debated efficacy include theophylline, anticholinergics, and magnesium sulfate. Heliox and noninvasive positive pressure ventilation are promising adjuncts to the treatment of nonintubated patients. In patients requiring intubation and mechanical ventilation, a ventilatory strategy should be used that avoids excessive lung hyperinflation by prolonging expiratory time. In many cases, this strategy requires acceptance of hypercapnea and high peak airway pressures. Patients should be aggressively sedated to decrease the need for muscle paralysis and the risk of post paralytic myopathy. Indirect evidence suggests that the current approach to mechanical ventilation in acute severe asthma decreases morbidity and mortality; however, the key to the management of this disease (which in many cases represents a failure of outpatient management) is patient education and disease prevention. Received: 25 October 1996 Accepted: 13 November 1996     

Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis

Abstract

Objectives: Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the small intrahepatic bile ducts disproportionally affecting women. Timely diagnosis and treatment can often prevent progression to liver cirrhosis. We hypothesized PBC diagnosis in male patients is delayed and prognosis impaired. We, therefore, conducted a case–control study and compared clinical and prognostic features among male and female patients with PBC.

Materials and methods: 49 male patients with PBC treated at a German tertiary care center between 2006 and 2017 were identified and compared to 98 age-matched female controls. Prospectively collected clinical/biochemical data were analyzed retrospectively. Liver biopsies were scored in a blinded fashion. Prognostic parameters were calculated using established prognostic scores (GLOBE, PBC-UKE). Statistical analysis was performed using Mann-Whitney test and Fisher´s exact test.

Results: At PBC diagnosis, male patients reported significantly less PBC-associated symptoms as compared to female controls (34 versus 71%, p?<?.01). Compared to female patients, median time from onset of PBC-related symptoms and/or first reported elevated cholestatic biochemical parameters to PBC diagnosis was significantly increased in men (36 versus 12?months, p?=?.02). In addition, male patients underwent liver biopsy to establish PBC diagnosis more frequently, tended to show more advanced fibrosis and showed significantly poorer prognostic PBC score results. Hepatocellular carcinoma was only observed in male patients (n?=?3).

Conclusions: When compared to women, men with PBC suffer from less PBC-related symptoms, receive PBC diagnosis delayed and have a worse prognosis. Despite its rarity, the diagnosis of PBC should be considered in men with elevated cholestatic parameters.     

Spirometry in the primary care setting: influence on clinical diagnosis and management of airflow obstruction

STUDY OBJECTIVE: To determine if screening spirometry in the primary care setting influences the physician's diagnosis and management of obstructive lung disease. DESIGN: Diagnosis and management assessed before and after the intervention of screening spirometry. PARTICIPANTS: A total of 1,034 patients who had ever smoked and were at least 35 years of age presenting to primary care practices for any reason. SETTING: Rural primary care practices. MEASUREMENTS AND RESULTS: Physicians were asked prior to and following presentation of spirometry test results if they thought airflow obstruction was present and if they planned to change management based on the results. A new diagnosis of unsuspected airflow obstruction was made by the physician in 93 patients (9%), and a prior diagnosis of airflow obstruction was removed after spirometry in 115 patients (11%). After viewing the spirometry results, physicians reported that they would change patient management in 154 patients (15%). Most planned management changes occurred when airflow obstruction was newly diagnosed (57 of 93 patients, 61%) and when the diagnosis of airflow obstruction remained unchanged (80 of 195 patients, 41%). A 6-month chart review documented the addition of respiratory medications in 8% of patients. CONCLUSION: Screening spirometry influences physicians' diagnosis of airflow obstruction and management plans especially in patients with moderate-to-severe obstruction.     

Sex differences in the presentation and course of asthma hospitalizations

OBJECTIVE: To distinguish between differences in prevalence, asthma severity, and treatment to explain sex-related differences in hospitalized asthma patients. DESIGN: Medical record review. SETTING: Thirty US hospitals as part of the University HealthSystem Consortium Asthma Clinical Benchmarking Project. PATIENTS: A random sample of patients aged 2 to 54 years and admitted to the hospital for acute asthma from 1999 to 2000. MEASUREMENTS: Demographics, medical history, initial oxygen saturation, initial peak expiratory flow (adults), initial pulmonary index (children), emergency department course, length of hospital stay, and discharge plans. RESULTS: The cohort included 606 pediatric (aged 2 to 17 years) and 680 adult (aged 18 to 54 years) inpatients. The sex ratio varied significantly by age: 40% were girls 2 to 17 years of age, and 68% were women 18 to 54 years of age p < 0.001). Among children, girls did not differ from boys according to asthma history, pulmonary index scores, or hospital length of stay. Among adults, women were more likely to have a primary care provider (90% vs 73%, p < 0.001) but did not differ according to asthma history or recent medication use. Women had a higher mean initial PEF compared to men (43% of predicted vs 36% of predicted, p < 0.001) and higher median initial oxygen saturation (95% vs 93%, p = 0.002) but did not differ by hospital length of stay. No sex differences in discharge regimens were identified in children or adults. CONCLUSIONS: Among US inpatients with acute asthma, male children are more common than female children, while women are more common in adults. The results in children are probably explained by prevalence differences, since no sex differences were seen in markers of asthma severity or treatment. In adults, increased symptoms in response to a given level of airway obstruction in women may contribute to the female predominance in asthma hospitalizations.     

Ethnic differences in the prevalence of pulmonary airflow obstruction among grain workers

World Health Organization data suggest that British males over 45 have a higher death rate from chronic bronchitis, emphysema, and asthma combined than do other Europeans. Although widely supposed that this is due to particularly unfavorable environmental factors in the British Isles, as well as a higher rate of tobacco consumption, ethnicity itself may be a significant factor in determining risk of obstructive airways disease. To test this hypothesis, we have analyzed the prevalence of airflow obstruction (100 x FEV1:FVC less than 68% and FEV1 less than 84 percent predicted) in Saskatchewan grain workers of British, German, and Eastern European ancestry using the Mantel-Haenszel odds ratio (OMH) and stepwise logistic regression. We found that the British grain workers had a significantly greater prevalence of airflow obstruction (OMH = 3.2; p less than 0.01) than the Eastern Europeans. We also found that ethnic origin made a significant contribution to the estimation of risk of airflow obstruction among grain workers independent of the effects of age and smoking.     

Acute mechanical bowel obstruction： Clinical presentation, etiology, management and outcome

AIM： To identify and analyze the clinical presentation, management and outcome of patients with acute mechanical bowel obstruction along with the etiology of obstruction and the incidence and causes of bowel ischemia, necrosis, and perforation.
METHODS： This is a prospective observational study of all adult patients admitted with acute mechanical bowel obstruction between 2001 and 2002.
RESULTS： Of the 150 consecutive patients included in the study, 114 （76%） presented with small bowel and 36 （24%） with large bowel obstruction. Absence of passage of flatus （90%） and/or feces （80.6%） and abdominal distension （65.3%） were the most common symptoms and physical finding, respectively. Adhesions （64.8%）, incarcerated hernias （14.8%）, and large bowel cancer （13.4%） were the most frequent causes of obstruction. Eighty-eight patients （58.7%） were treated conservatively and 62 （41.3%） were operated （29 on the first day）. Bowel ischemia was found in 21 cases （14%）, necrosis in 14 （9.3%）, and perforation in 8 （5.3%）. Hernias, large bowel cancer, and adhesions were the most frequent causes of bowel ischemia （57.2%, 19.1%, 14.3%）, necrosis （42.8%, 21.4%, 21.4%）, and perforation （50%, 25%, 25%）. A significantly higher risk of strangulation was noticed in incarcerated hernias than all the other obstruction causes.
CONCLUSION： Absence of passage of flatus and/or feces and abdominal distension are the most common symptoms and physical finding of patients with acute mechanical bowel obstruction, respectively. Adhesions, hernias, and large bowel cancer are the most common causes of obstruction, as well as of bowel ischemia, necrosis, and perforation. Although an important proportion of these patients can be nonoperatively treated, a substantial portion requires immediate operation. Great caution should be taken for the treatment of these patients since the incidence of bowel ischemia, necrosis, and perforation is significantly high.     

Sex differences in clinical presentation,severity and outcome of stroke: Results from a hospital-based registry

Background and purposeSex related differences in cardiovascular disease and stroke are issues of increasing interest. The aim of this study was to evaluate for sex differences in clinical presentation, severity of stroke and outcome in a population of patients admitted to 4 public and 1 private hospitals in three different regions of Italy.MethodsAll hospital admissions for ischemic and haemorrhagic stroke (ICD-IX code 434 and 431 respectively) between January 1st and December 31st, 2011 at five different hospitals located in three different regions of Italy: Milan (North), Rome and Perugia (Center), and Palermo (South) have been recorded and sex-differences have been evaluated.ResultsA total of 1272 stroke patients were included in the analysis: 1152 ischemic and 120 haemorrhagic strokes, 567 women and 705 men. Compared to men, women were significantly older (mean age 75.2 SD 13.7 vs 71.5 SD 12.5 years, P < 0.001) and their stroke severities at onset, measured by NIHSS, were also compared to men (10 SD 8 vs 8 SD 7, P < 0.001).Female sex was associated with a worse functional prognosis measured by modified Rankin Scale score (mRS ≥ 3), as well as in-hospital mortality, without reaching statistical significance.There were no observed significant differences between sexes regarding the number of patients treated with thrombolytic therapy. Analysis of the distribution of risk factors between sexes showed a prevalence of atrial fibrillation in women (29% vs 21%, P = 0.003).ConclusionsBoth stroke severity and functional outcome were worse in women.     

Lack of age-related differences in the clinical presentation of digoxin toxicity.

BACKGROUND--Digoxin toxicity occurs most commonly among the elderly. While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known. METHODS--We performed secondary analysis of data from a postmarketing surveillance study of patients with life-threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function. RESULTS--The prevalence of high-degree atrioventricular block showed an increasing but nonsignificant trend with age (40%, 40%, 42%, and 47%, respectively). Age-related trends in high-degree atrioventricular block were stronger among men than women and even stronger among men with underlying cardiac ischemia. The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively). There were no age-related differences in degree of renal impairment or maintenance dose, but maintenance dose decreased with increasing renal impairment. CONCLUSIONS--Among patients with life-threatening digoxin toxicity, there is no age-related difference in clinical presentation.     

Bronchial reactivity and airflow obstruction in rheumatoid arthritis.

OBJECTIVES--To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The control population consisted of patients attending the rheumatology department for minor degenerative joint problems. METHODS--One hundred patients with rheumatoid arthritis (RA) [72 (72%) women, 28 (28%) men; mean (SD) age 58 (10) years] and fifty controls [30 (60%) women, 20 (40%) men; mean (SD) age 56 (9) years] were studied. Detailed medical, smoking and drug histories were taken; skin prick tests were performed to assess atopy and chest and hand radiographs were performed. Spirometry, flow volume loops and gas transfer factor measurement were performed to detect airflow obstruction and methacholine inhalation tests were carried out to assess bronchial reactivity. RESULTS--There was no significant difference between rheumatoid arthritis patients and the controls in age, sex, smoking status and atopy on skin prick testing (p < 0.05). A significantly higher number of patients with RA had a history of wheeze compared with the controls (18% v 4%, p < 0.05). FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower in the rheumatoid arthritis group (p < 0.05). A significantly higher number of patients with RA compared with controls showed bronchial reactivity to inhaled methacholine [55 (55%) v 8 (16%), p < 0.05]. FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower among the patients with RA achieving PD20 FEV1 to inhaled methacholine (p < 0.05). CONCLUSION--In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.     

Sex, age, and clinical presentation of acute coronary syndromes.

AIM: To investigate sex differences in clinical presentation in younger and older patients hospitalised with a wide spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: We analysed 10253 patients with a discharge diagnosis of ACS in the Euro Heart Survey of patients with Acute Coronary Syndromes. There were 1010 women and 3709 men < 65 years. Among patients <65 years, fewer women than men presented with ST elevation, (OR [odds ratio]: 0.62 [0.53-0.71]) and developed Q-wave myocardial infarction (OR 0.58 [0.50-0.67]), whereas in patients > or =65 years there was no significant sex difference. Women <65 years were more likely than men of the same age to be discharged with a diagnosis of unstable angina (OR 1.56 [1.35-1.79]), but there was no sex difference in older patients; the p for interaction between sex and age for both was <0.0001. Among patients who underwent coronary angiography, both younger and older women were less likely than men to have 3-vessel or main stem disease. In a logistic regression analysis stratified for age, female sex was a significant negative determinant of presenting with ST elevation in patients <65 years (OR 0.68 [0.58-0.79]), whereas there was no effect of sex in patients > or =65 years. CONCLUSION: In younger patients with ACS, women were less likely than men to present with ST elevation and more likely to be discharged with a diagnosis of unstable angina. In older patients there were no differences in clinical presentation. Both older and younger women had less extensive atherosclerosis. The findings suggest a different pathophysiology of ACS in younger, but not older, women.     

Reversible airflow obstruction: clinical spectrum and responsiveness to anticholinergic drugs

In order to delineate the clinical profiles which correspond to different patterns of responsiveness to inhaled anticholinergic drugs (i.e. atropine methonitrate, ipratropium bromide), 102 subjects tested with these drugs and with beta 2-adrenergic bronchodilators were classified into three groups, namely: a group with positive skin prick tests (group 1), a group with blood or sputum eosinophilia but negative skin prick tests (group 2), and a group with negative skin prick tests and neither blood nor sputum eosinophilia (group 3). All had reversible airflow obstruction and their clinical profiles closely corresponded to atopic asthma, non-atopic asthma and chronic bronchitis, respectively, but the prevalence of mucus hypersecretion was similar in all three groups. Pharmacologically, group 1 patients were distinguished from the other two groups by their significant impairment of 1-second forced expiratory volume response to the bronchodilator action of anticholinergic drugs. This is the physiological correlate of atopic asthma.     

Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy

OBJECTIVES: The goal of this study was to assess gender-related differences in a multicenter population with hypertrophic cardiomyopathy (HCM). BACKGROUND: Little is known regarding the impact of gender on the heterogeneous clinical profile and clinical course of HCM. METHODS: We studied 969 consecutive HCM patients from Italy and the U.S. followed over 6.2 +/- 6.1 years. RESULTS: Male patients had a 3:2 predominance (59%), similar in Italy and the U.S. (p = 0.24). At initial evaluation, female patients were older and more symptomatic than male patients (47 +/- 23 years vs. 38 +/- 18 years; p < 0.001; mean New York Heart Association [NYHA] functional class 1.8 +/- 0.8 vs. 1.4 +/- 0.6; p < 0.001), and more frequently showed left ventricular outflow obstruction (37% vs. 23%; p < 0.001). Moreover, female patients were less often diagnosed fortuitously by routine medical examination (23% vs. 41% in male patients, p < 0.001). Female gender was independently associated with the risk of symptom progression to NYHA functional classes III/IV or death from heart failure or stroke compared with male gender (independent relative hazard 1.5; p < 0.001), particularly patients > or =50 years of age and with resting outflow obstruction (p < 0.005). Hypertrophic cardiomyopathy-related mortality and risk of sudden death were similar in men and women. CONCLUSIONS: Women with HCM were under-represented, older, and more symptomatic than men, and showed higher risk of progression to advanced heart failure or death, often associated with outflow obstruction. These gender-specific differences suggest that social, endocrine, or genetic factors may affect the diagnosis and clinical course of HCM. A heightened suspicion for HCM in women may allow for timely implementation of treatment strategies, including relief of obstruction and prevention of sudden death or stroke.     

Gender-related differences in the clinical presentation of malignant and benign pheochromocytoma

Signs and symptoms associated with pheochromocytomas are predominantly caused by catecholamine excess, but tend to be highly variable and non-specific. In this study, we evaluated 23 male and 35 female pheochromocytoma patients for symptoms and signs of pheochromocytoma with special regard to gender-related differences in presentation. Total symptom score comparison between genders showed significant differences (12.0 vs. 7.8, P-value 0.0001). Female patients reported significantly more headache (80% vs. 52%), dizziness (83% vs. 39%), anxiety (85% vs. 50%), tremor (64% vs. 33%), weight change (88% vs. 43%), numbness (57% vs. 24%), and changes in energy level (89% vs. 64%). Females and males displayed comparable biochemical phenotypes (60% and 65% noradrenergic phenotype, respectively). Use of alpha- and/or beta-blockade between males and females did not differ significantly. Subgroup analyses and multiple regression analysis revealed gender differences to be irrespective of benign or malignant disease, use of adrenoceptor-blockade, age and biochemical phenotype. We conclude female patients have significantly more self-reported pheochromocytoma signs and symptoms than male patients irrespective of biochemical phenotype and tumor presentation which may be related to distinct catecholamine receptor sensitivity. Clinicians should be aware of these complaints in female pheochromocytoma patients and offer adequate treatment if indicated.     

Regional differences in risk factors and clinical presentation of diabetic foot lesions.

BACKGROUND: Problems associated with the diabetic foot are worldwide. However, there may be regional variation among risk factors and clinical presentation. Prospective comparative data concerning this topic are rare. AIM: To determine differences in underlying risk factors and clinical presentation of foot problems among people with diabetes in different regions. PATIENTS AND METHODS: Six hundred and thirteen consecutive patients with diabetic foot lesions from three centres [Soest-Germany (GER), Dar-es-Salaam, Tanzania (TAN) and Chennai, India (IND)] were included during the period June 1998 through December 1999. Diabetes-related data, risk-factor profiles, and lesion-related data were collected for each patient. Due to varying proportions of recurrent lesions among the centres, only data from patients with newly presenting diabetic foot lesion were analysed. RESULTS: Of the 613 patients sampled, 368 (60%) were treated for newly presenting diabetic foot lesion. In all three centres, patients were predominately male and had Type 2 diabetes. The average diabetes duration until the onset of the initial foot lesion was 14 years in GER and 12 years in IND, but only 5 years in TAN. The corresponding patient ages were 71, 56 and 51 years. Neuropathy was common to patients in all three centres. Peripheral vascular disease (PVD) was a frequent risk factor in GER (48%). In TAN and IND it was far less common (12 and 13%), probably due to younger patient populations, shorter diabetes duration and lower proportions of smokers. Inadequate footwear was the most common cause of foot lesions in GER (19%), while lack of footwear, irregular foot care and burns were the primary precipitating factors among patients in TAN and IND. CONCLUSION: Similarities in different regions of the world among people with diabetes suffering newly presenting foot lesions include a predominance of males and patients with Type 2 diabetes, as well as a high frequency of diabetic neuropathy. However, differences concerning age, diabetes duration, peripheral vascular disease, and precipitating factors contributing to injury are also observed.     

Asthma vs. non-specific reversible airflow obstruction: clinical features and responsiveness to anticholinergic drugs

85 subjects with 20% reversibility in FEV1 were classified into the categories of asthma (55 patients) and non-specific airflow obstruction (30 patients), respectively, on the basis of the presence or absence of eosinophilia (in the blood or sputum). Asthmatics were further subdivided into the atopic and non-atopic subgroups, respectively, on the basis of skin prick tests. Clinically, paroxysmal nocturnal wheezing was more significantly associated with asthma than with non-specific airflow obstruction. Atopic asthmatics were distinguished from patients with non-specific airflow obstruction by their younger age at presentation and at onset of obstructive symptoms, by a history of allergic provocation of wheezing, a family history of asthma and other atopic diseases, and by a lower incidence of mucus hypersecretion. The last 3 symptoms also distinguished atopic from non-atopic asthma. Furthermore, unlike patients with non-atopic asthma or patients with non-specific airflow obstruction, atopic asthmatics had a significant impairment of bronchodilator responsiveness to inhaled anticholinergic drugs.     

Effect of diuretics on cardiopulmonary performance in severe chronic airflow obstruction. A controlled clinical trial

In a randomized, controlled trial, ten patients with pulmonary heart disease due to severe chronic airflow obstruction were stratified into two groups: group 1 had clinical features of congestive heart failure during respiratory failure and were regularly receiving diuretics; group 2 had no such clinical features and were not receiving diuretics. In group 1, when placebo was substituted for diuretics, pulmonary edema developed in three patients; exercise performance and ventricular function of the remaining two patients deteriorated. In group 2, there was no difference in exercise tolerance or ventricular function between placebo and diuretic therapy. The clinical deterioration in group 1 was related to abnormal left ventricular function. Thus, diuretics benefit only patients who have clinical features of congestive heart failure. In patients with isolated abnormal right ventricular function, diuretics may be harmful.