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Background: Inpatient beta-lactam allergy labels may increase the unnecessary use of aztreonam and non-beta-lactam antibiotics, which can then lead to more adverse events and increased health care costs, OBJECTIVE: To assess the impact of a novel 2-step process (medication history review followed by risk stratification) on rates of beta-lactam delabeling, aztreonam use, and desensitizations on pediatric, adult, and obstetrics inpatients at a tertiary academic center., Methods: We prospectively collected data on 700 patients who received inpatient consultation from the Beta-Lactam Allergy Evaluation Service between August 2021 and July 2022. Patients were delabeled either by medication review alone, drug challenge alone if with a low-risk history, or penicillin skin test followed by drug challenge if with a high-risk history. Generalized linear regression modeling was used to compare aztreonam days of therapy in the intervention year with the 2 prior years. Drug desensitizations were assessed by electronic chart review., Results: Most of the patients (n = 656 of 700, 94%) had more than or equal to 1 beta-lactam allergy label removed, clarified, or both; 77.9% of these patients (n = 511 of 656) had 587 beta-lactam allergy labels removed. Nearly one-third (n = 149, 27.6%) had 162 allergy labels removed solely by medication history review. All 114 penicillin skin tests performed had negative results, and 98% (8 of 381) of the patients who underwent any drug challenge passed. Only 5.7% of the delabeled patients were relabeled. There was a 27% reduction in aztreonam use (P = .007). Beta-lactam desensitizations were reduced by 80%., Conclusion: A full-time inpatient beta-lactam allergy service using medication history review and risk stratification can safely and effectively remove inpatient beta-lactam allergy labels, reduce aztreonam use, and decrease beta-lactam desensitizations., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary angioedema (HAE) is a rare condition characterized by potentially fatal, recurrent episodes of painful swelling. Whereas there are limited studies evaluating the quality of life of individuals with HAE, none have evaluated the impact of HAE on older adults., Objective: To evaluate the effect of HAE on older adults through qualitative methodology., Methods: A group of 3 physicians with extensive research and clinical experience in HAE developed a focus group guidebook highlighting issues of importance to older adults. A total of 17 patients with HAE (type I or II) aged 60 years and older participated in focus groups. Three independent reviewers coded each focus group transcript using a thematic saturation approach., Results: Reviewers identified 7 core themes from the focus groups. The themes identified encompassed the following: (1) challenges with securing medications and insurance concerns; (2) the experience of living with HAE before the advent of newer and more effective therapeutic options; (3) a worsening of HAE attack frequency and severity with aging; (4) the effects of comorbid conditions such as arthritis, memory loss, and irritable bowel syndrome; (5) changes in HAE with menopause; and (6) changing perspective on HAE with age, the effect of HAE on interpersonal relationships including the decision to have children, and goals for future care and research including support groups and a desire to be included in clinical trials., Conclusion: Older adults with HAE have specific challenges and concerns that may be unique compared with younger populations. Health care providers should address these to provide optimal care., Competing Interests: Disclosures Dr Baptist reports receiving research and consulting support from BioCryst and Takeda. Dr Craig reports research conflicts with BioMarin, Kalvista, Pharvaris, GlaxoSmithKline, CSL Behring, Takeda, Ionis, Intellia, AstraZeneca, Pfizer, Regeneron, and Grifols; speaking conflicts with Takeda, CSL Behring, and Grifols; is a consultant for BioMarin, Intellia, CSL Behring, Takeda, BioMarin, Ionis, AstraZeneca, Kalvista, CSL Behring, and BioCryst; has center designations from the International Hereditary Angioedema Association and Alpha-1 (HAE-A) Foundation; and is a member of the medical advisory board for the HAE-A. Dr Riedl reports receiving research support from BioCryst, BioMarin, CSL Behring, Ionis, Kalvista, Pharvaris, and Takeda; consulting fees from Astria, BioCryst, BioMarin, CSL Behring, Cycle, Intellia, Kalvista, Ono Pharma, Pharming, Pharvaris, and Takeda; honoraria for speaker presentations from CSL Behring, Pharming, and Takeda; and is a member of the US HAE-A medical advisory board. The other authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary angioedema (HAE) is a rare and potentially fatal genetic disease associated with recurrent and unpredictable episodes of angioedema. Although modern therapies have dramatically increased quality of life, insurance changes, delays, and denials are becoming more common., Objective: To examine the impact of insurance delays and denials on patient health and well-being., Methods: A total of 20 patients with HAE (type 1 and 2) who recently experienced insurance delays or denials completed an online survey, and 19 participated in a follow-up focus group. The survey and focus group addressed the impact of insurance challenges on the use of health care services, work/school attendance, and anxiety. Three independent reviewers coded each focus group transcript using a thematic saturation approach., Results: A total of 70% of participants reported an increased frequency of angioedema attacks resulting from insurance delays or denials. More than 50% missed work/school days because of increased attacks, and 90% reported greater anxiety. Twenty-five percent of respondents reported more urgent care or emergency department visits. In focus groups, participants identified specific ways that losing access to medication had a negative impact on their health, family, and work/school life. Insufficient notification of health insurance policy changes and the time and effort required to regain access to medications compounded patients' frustration and anxiety., Conclusion: Insurance delays and denials have significant impacts on individuals with HAE including (1) increased urgent care and emergency department visits, (2) missed work/school days, (3) higher levels of anxiety, and (4) a negative impact on family life., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: A newly approved, high-sensitivity troponin T (hsTnT) assay may offer opportunities to more rapidly assess for acute coronary syndrome and identify lower thresholds of myocardial injury. As more emergency departments begin to use the hsTnT assay, anticipating barriers to hsTnT implementation success are critical to realizing potential benefits in rapid, accurate patient assessment., Methods: At a tertiary health system emergency department, hsTnT was implemented along with a diagnostic algorithm and a decision tree to aid in utilization. Qualitative interviews with 18 physicians and advance practice providers were conducted 2 months' postimplementation and again 4 to 6 months postimplementation to capture clinician perceptions to hsTnT implementation efforts. Deductive coding was performed using implementation science determinants frameworks to identify emerging themes related to this topic., Results: Four themes emerged from the interviews: 1) the need for additional clinician education, 2) challenges with care handoffs, 3) lack of buy-in from the hospital community, and 4) key successes., Conclusion: Interviews demonstrated that implementation of hsTnT was associated with several implementation barriers from the perspective of emergency department clinicians. Future implementation efforts should focus on diverse and sustained staff educational efforts, models that address challenges with care handoffs between emergency department clinicians and inpatient clinicians, and operational teams that include inpatient clinicians to facilitate buy-in., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Firearm-related deaths remain a top cause of mortality in American children and adolescents. In a 2012 policy statement, the American Academy of Pediatrics urged pediatricians to incorporate questions about the availability of firearms into their patient history taking. We aim to evaluate the frequency of screening for home firearms in an academic tertiary-care hospital inpatient setting., Methods: This retrospective chart review examined patients with the following pediatric diagnoses admitted to a tertiary-care pediatric hospital from 2006 to 2015: asthma, bronchiolitis, cellulitis, jaundice, single liveborn infant, bacterial and viral pneumonia, and all mood disorders. Data analysts then searched the patient charts that met these inclusion criteria for documentation of firearm screening as indicated by use of the terms "firearm," "pistol," "gun," "handgun," "bullet," "ammunition," or "rifle" in the admissions history and physical., Results: Evidence of screening for firearms in the home was found in 1196 of the 40 658 charts included in the study (2.94%). The most frequently screened diagnosis and admitting service were mood disorders and child psychiatry, respectively (1159 of 3107; 37.3%). Only 19.8% of identified gun-owning families received specific anticipatory guidance., Conclusions: Firearm screening and gun safety education occurred infrequently in the inpatient setting. Inpatient encounters may provide an opportunity for increased screening and education because the hospital environment also includes additional resources, exposure to a greater number of providers, and the presence of more family members or caregivers. Further studies are warranted to explore barriers to inpatient screening and possible mechanisms for improvement., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objectives: In 2015, the American Academy of Pediatrics (AAP) published an updated consensus statement containing 17 discharge recommendations for healthy term newborn infants. In this study, we identify whether the AAP criteria were met before discharge at a tertiary care academic children's hospital., Methods: A stratified random sample of charts from newborns who were discharged between June 1, 2015, and May 31, 2016, was reviewed. Of the 531 charts reviewed, 433 were included in the study. A review of each chart was performed, and data were collected., Results: Descriptive statistics for our study population ( N = 433) revealed that all 17 criteria were followed <5% of the time. The following criteria were met 100% of the time: clinical course and physical examination, postcircumcision bleeding, availability of family members or health care providers to address follow-up concerns, anticipatory guidance, first appointment with the physician scheduled or parents knowing how to do so, pulse oximetry screening, and hearing screening. These criteria were met at least 95% to 99% of the time: appropriate vital signs, regular void and stool frequency, appropriate jaundice and sepsis management, and metabolic screening. The following criteria were met 50% to 95% of the time: maternal serologies, hepatitis B vaccination, and social risk factor assessment. Four of the criteria were met <50% of the time: feeding assessment, maternal vaccination, follow-up timing for newborns discharged at <48 hours of life, and car safety-seat assessment., Conclusions: Our data reveal that the AAP healthy term newborn discharge recommendations are not consistently followed in our institution., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: We sought to determine the correlation between the probability of postoperative opioid prescription refills and the amount of opioid prescribed, hypothesizing that a greater initial prescription yields a lower probability of refill., Background: Although current guidelines regarding opioid prescribing largely address chronic opioid use, little is known regarding best practices and postoperative care., Methods: We analyzed Optum Insight claims data from 2013 to 2014 for opioid-naïve patients aged 18 to 64 years who underwent major or minor surgical procedures (N = 26,520). Our primary outcome was the occurrence of an opioid refill within 30 postoperative days. Our primary explanatory variable was the total oral morphine equivalents provided in the initial postoperative prescription. We used logistic regression to examine the probability of an additional refill by initial prescription strength, adjusting for patient factors., Results: We observed that 8.67% of opioid-naïve patients refilled their prescriptions. Across procedures, the probability of a single postoperative refill did not change with an increase with initial oral morphine equivalents prescribed. Instead, patient factors were correlated with the probability of refill, including tobacco use [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.23-1.57], anxiety (OR 1.30, 95% CI 1.15-1.47), mood disorders (OR 1.28. 95% CI 1.13-1.44), alcohol or substance abuse disorders (OR 1.43, 95% CI 1.12-1.84), and arthritis (OR 1.21, 95% CI 1.10-1.34)., Conclusions: The probability of refilling prescription opioids after surgery was not correlated with initial prescription strength, suggesting surgeons could prescribe smaller prescriptions without influencing refill requests. Future research that examines the interplay between pain, substance abuse, and mental health could inform strategies to tailor opioid prescribing for patients.

Aim: Identify the behavioral challenges to the use of genome sequencing (GS) in a clinical setting., Materials & Methods: We observed how general internists and nongenetic specialists delivered GS results to patients enrolled in the MedSeq Project. Using transcripts of such disclosure interactions, we made qualitative observations of communication behaviors that could limit the usefulness of GS results until reaching the point of thematic saturation., Results: Findings included confusion regarding genomic terminology, difficulty with the volume or complexity of information and difficulties communicating complex risk information to patients. We observed a broad dismissal of clinical value of GS by some physicians and sometimes ineffective communication regarding health behavior change., Conclusion: Overcoming these behavioral challenges is necessary to make full use of clinical GS results., Competing Interests: Financial & competing interests disclosure The MedSeq Project is carried out as a collaborative study supported by the National Human Genome Research Institute U01-HG006500. Dr. Robert C Green receives compensation for speaking or consultation from AIA, GenePeeks, Helix, Illumina, Ohana, Prudential and Veritas; and is co-founder, advisor and equity holder in Genome Medical, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Identifying the etiology of a cutaneous eruption in the setting of an acute cluster outbreak is of utmost importance due to the inherent potential public health impact. The differential diagnosis ranges from innocuous arthropod bites to more concerning causes such as infection, medication reaction, and environmental exposure. We report the simultaneous presentation of 15 US Marines who presented with numerous discrete papular skin eruptions. Subsequent thorough patient evaluation and history, literature review, immunization status reconciliation, entomological assessment, site survey, and skin biopsy were performed. This case series is one of the largest reported to date of a cluster outbreak of a papular dermatitis secondary to bites from thrips (ie, insects of the order Thysanoptera).

Lupus erythematosus tumidus (LET) is a photosensitive skin disease characterized by succulent, edematous, and non-scarring plaques. Histologic features include perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. Despite being first described in 1909, there are few case reports in the current literature describing this disease and even fewer that discuss treatment. We describe a case of a 22-year-old woman with systemic lupus erythematosus (SLE) and secondary class V lupus nephritis. She was referred to Dermatology for an intermittent pruritic facial eruption that was clinically and histologically consistent with LET. There is much controversy in literature as to whether or not LET is a unique variant of cutaneous lupus erythematosus. Interestingly, the mainstay of treatment for LET, in the limited case reports and series that exist, is with antimalarial drugs, which our patient had already been taking for SLE. This case exemplifies the need for complete disease characterization, evidence-based treatment, and a multidisciplinary approach.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal severe cutaneous reaction, which has a delayed onset after the initiation of an inciting medication. After recognition and withdrawal of the causative agent, along with aggressive management, a majority of patients will have complete recovery over several months. We present a rare case of DRESS secondary to oxcarbazepine with an elevated human herpesvirus-6 titer.

Opportunistic infections following immunosuppression in solid organ transplant (SOT) patients are common complications with the skin being a common sight of infection. Nontuberculous mycobacteria (NTM) are rare but potential causes of skin infection in SOT patients. We present a case of an adult male immunosuppressed following renal transplantation who presented with an asymptomatic rash for several months. The patient's skin eruption consisted of erythematous papules and plaques coalescing into an annular formation. After failure of the initial empiric therapy, a punch biopsy was performed that demonstrated nerve involvement suspicious for Mycobacterium leprae. However, culture of the biopsy specimen grew acid-fast bacilli that were subsequently identified as M. haemophilum. His rash improved after a prolonged course of clarithromycin and ciprofloxacin. Both organisms are potential causes of opportunistic skin infections and can be difficult to distinguish with similar predilection for skin and other biochemical and genetic similarities. Ultimately they can be distinguished with culture as M. haemophilum will grow in culture and M. leprae will not. This case was unique due to nerve involvement on biopsy which is classically seen on biopsies of leprosy.

Background: Although platelet-rich plasma (PRP) has been extensively studied for over a decade, there are no definitive reports, which prove the benefit of using PRP in sinus augmentation procedures. In addition, no systematic literature review has been done to report the benefit of treatment outcome in patients who received PRP in conjunction with bone/bone substitutes in maxillary sinus augmentation procedures. Therefore, it can be rightly stated that evidence for an adjunctive benefit of using PRP with bone grafts in sinus augmentation procedures is equivocal and inconclusive., Aim: : The objective of this systematic literature review was to examine this literature in determining whether PRP with bone and bone substitutes leads to more rapid and effective bone regeneration clinically, radiographically, and histologically with sinus augmentation procedures and was there any clinical data parallel to animal experiments providing clinical evidence in sinus augmentation procedures?, Methods: A systematic review of randomized clinical trials of at least 6 months duration was conducted comparing PRP and bone/bone substitutes (test group) to bone/bone substitutes (control group) alone. Electronic databases such as MEDLINE and CENTRAL (Cochrane central register of controlled clinical trials) were searched for relevant articles. The reference list of all included articles was searched along with unpublished clinical trials whose abstracts were available., Results: Although, there is a lack of human studies, which show benefit of using PRP in conjunction with bone grafting materials, it can be stated that use of PRP does lead to early regeneration and reduction in healing time of soft and hard tissues. However, no significant statistical or clinical benefit was reported from studies that would satisfy the inclusion criteria. This study answers the question very clearly that at this point of time, there is no human study that strongly supports the benefit of using PRP in sinus augmentation procedures., Conclusion: There is a paucity of clinically controlled trials regarding benefits of PRP in sinus augmentation procedures. Theoretically, it seems to have significant beneficial effects on the soft and hard tissue healing; however, the disparity in study design, surgical techniques, and different outcome assessment variables used, makes it difficult to assess the practical benefit of its clinical use. Although no obvious positive effects of PRP on healing of bone graft material in maxillary sinus augmentation procedures were noted, the handling of the particulate bone grafts was improved.

Platelet-rich plasma (PRP) is an autologous concentration of platelets in concentrated plasma, which is extensively used to promote soft and hard tissue healing. The significance behind its use refers to the abundance of growth factors present in a well-prepared PRP concentrate. These growth factors enhance the rate and quality of wound healing by different mechanisms. The objective of this review article is to explain the biological aspect of hard and soft tissue healing by application of PRP in conjunctions with its molecular basis.

The authors examined the relationship between calcified coronary atherosclerosis and an array of cardiovascular risk factors in sequential logistic models to determine the extent to which these markers overlap in their identification of patients at risk for developing coronary heart disease. The prevalence of coronary artery calcium using electron beam computed tomography was 19.4% in this cross-sectional study of a prospective, consecutive, screening cohort of 1999 healthy United States Army personnel (aged 39-50 years). The proportion of the total variance of coronary artery calcium explained by sequential logistic models incorporating conventional, emerging, hereditary, lifestyle, and psychosocial cardiovascular risk variables increased progressively from 9.7% to 14.5%. The best-fit logistic model for the prediction of coronary artery calcium identified age, male gender, Framingham risk score, total cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, a family history of coronary heart disease, white race, physical inactivity, and lower depression scores as significant independent correlates of coronary artery calcium. These data indicate that the explanatory power of models for atherosclerosis can be significantly improved with the use of emerging, heredity, lifestyle, and psychosocial factors. The large residual variance, however, supports the potential of atherosclerosis imaging to incrementally and independently identify coronary heart disease risk.

Incident chest pain occurred in 30.3% of 1,743 asymptomatic healthy men and women who were followed for up to 4 years. Proportions of patients who had coronary artery calcium were similar among those who had no chest pain, noncardiac pain, atypical pain, or cardiac chest pain. Incident chest pain is common and should be examined according to a patient's pretest probability of developing coronary artery disease, without excessive influence of the presence of coronary artery calcium.

Background: A 58-year-old female with a history of hypertension and asthma presented to an internist for a routine physical examination. A grade II/VI systolic ejection murmur and electrocardiogram abnormalities were noted. She was referred to a cardiologist for further assessment., Investigations: Transthoracic echocardiography, transesophageal echocardiography, contrast-enhanced CT and MRI, exploratory laparotomy., Diagnosis: Intracardiac leiomyomatosis., Management: Surgical excision.

This case illustrates the complementary value of transesophageal echocardiography to routine transthoracic echocardiography in an asymptomatic adult patient with Turner's syndrome. The combined findings of bicuspid aortic valve, severe aortic dilation, coarctation of the aorta, and type A aortic dissection were clearly delineated by transesophageal echocardiography.

The pulmonary manifestations of 5 biopsy-proved cases of lymphomatoid granulomatosis are discussed. Two patients had diffuse reticulonodular infiltration of the lungs, thought to represent infiltrates of lymphomatoid granulomatosis. Three had nodular densities of varying size and distribution, with radiologically normal intervening lung, and biopsy suggested that these represented infarcts; the actual infiltrates of lymphomatoid granulomatosis were below the limits of resolution of the chest radiograph.

We studied the power spectrum of the diaphragm electromyogram (EMG) at frequencies between 31 and 246 Hz in four young normal subjects and five patients with chronic obstructive lung disease (COPD). Diaphragm EMGs were analyzed during spontaneous breathing and maximum inspiratory efforts to determine the effect of signal-to-noise ratio on the power spectrum and if treadmill exercise to dyspnea was associated with diaphragm fatigue. We found that the centroid frequencies of the power spectra (fc) were strongly correlated (r = 0.93) with ratios of power at high frequencies to power at low frequencies (H/L) for all subjects. Of the two indices, H/L had the largest standard deviation expressed as a percentage of the mean. The mean values of both of these decreased significantly after exercise, fc from 100.2 to 97.3 and H/L from 1.07 to 0.97. Signal-to-noise ratios were higher in maximal inspiratory efforts and after exercise in normal subjects and higher in COPD patients. The signal-to-noise ratio was correlated negatively with fc and H/L, indicating that these indices of the shape of the power spectrum are influenced by signal strength and noise levels as well as muscle function. We conclude that the fc and H/L index similar qualities of the power spectrum, that they are partially determined by the signal-to-noise ratio, and that, in some cases, exercise to dyspnea is associated with apparently mild diaphragm fatigue.

To assess the consequences to the human diaphragm of alterations in body weight and muscularity, we measured the mass, thickness, area, and length of diaphragm muscle at necropsy. Of 33 subjects who were clinically well until sudden death, 27 had sedentary occupations and normal weight (group N), while 6 were nonobese laborers whose average weight was 40% greater than normal (group M). Among 37 patients dying of more prolonged illness, 23 were of normal weight (group W), while 14 weighed 71% of normal (group U). Subjects with obesity, chronic pulmonary disease, or edema were excluded. Disease per se did not significantly affect diaphragm dimensions. However, in group M diaphragm muscle mass, thickness, area, and length were 165, 129, 125, and 117% of normal (P less than 0.005), whereas in group U the corresponding values were 57, 73, 77, and 83% (P less than 0.001). Thus alterations in body weight and muscularity profoundly affect diaphragm muscle mass, causing a nearly threefold variation between muscular normal subjects and underweight patients.

Thirty-two patients with pleural effusions (7 malignant, 5 with connective tissue disease, 5 with infections, 9 idiopathic, 6 miscellaneous) were studied to determine if immune complex formation might be involved in the pathogenesis of pleural fluid formation. Immune complexes were detected in serum, pleural fluid and in parietal pleural capillaries using direct immunofluorescence in the following groups: malignant disease (57%, 29%, 67%), connective tissue diseases (100%, 100%, 100%), infectious diseases (0%, 44%, 67%), idiopathic (67%, 44%, 75%), and miscellaneous (25%, 17%, 0%). Whereas the degree of immune complex was higher in serum than in pleural fluid in patients with malignant disease, the converse was true in patients with connective tissue diseases. Activation of C3 and properdin factor B was almost invariable in pleural fluid from patients with connective tissue disease and bacterial infections. These data suggested that pleural immune complexes are frequently associated with exudative pleural effusions. Immune complexes may lead to formation of pleural fluid by increasing capillary permeability. This may result from either a local Arthus-type reaction within the pleura, local immune complex formation within pleural fluid leading to release of inflammatory mediators, and/or deposition of circulating immune complexes in pleural vessels.

To assess the effect of COPD on diaphragm muscle dimensions, we measured diaphragm muscle mass, thickness, area, and lengths in 18 COPD patients at necropsy. We compared these results with data obtained from 22 non-COPD patients matched with regard to age, height, weight, and sex distribution. In the COPD patients, diaphragm muscle mass was 213 +/- SD 69 g, thickness was .320 +/- .055 cm, area was 647 +/- 160 cm2, coronal muscle length was 27.8 +/- 4.0 cm and sagittal muscle length was 15.8 +/- 2.8 cm. These values were within +/- 8 percent of the comparable values in the non-COPD patients, with no significant differences. There was no correlation between diaphragm length and lung volume in 13 COPD patients with TLC and ten with RV measurements. We conclude that over the range of lung volume encountered (TLC 135 +/- 28 percent predicted, RV 102 +/- 29 percent predicted TLC), there is no evidence for permanent shortening of the diaphragm.

To assess the effects of airway conductance (Gaw) and respiratory muscle strength (RMS) on maximal voluntary ventilation (MVV), we studied 8 normal subjects (N), 8 patients with interstitial lung disease (ILD), and 16 with chronic airflow limitation (CAL). In the patients with ILD, RMS explains 83% of the variance in MVV (p less than 0.005), but Gaw explains none. In the patients with CAL, Gaw and RMS explain, respectively, 65 and 34% of the variance in MVV (p less than 0.02). Considering Gaw and RMS together increases the explained variance to 77% (p less than 0.005). In groups CAL and N combined, Gaw and RMS explain 86% of the variance in MVV, with 71% explained by Gaw and 34% by RMS, which the other variable alone failed to explain (p less than 0.005). When the data are normalized for age, sex, height, and lung volume, the influence of %RMS on %MVV is halved, but remains significant (p less than 0.05). We conclude that RMS is a primary determinant of MVV in patients with ILD, and an important determinant in patients with CAL.

To characterize the in vivo force-length relation of the human diaphragm, we related pressures during static inspiratory efforts (Pmus and Pdi, respiratory muscle and transdiaphragmatic pressures, respectively) to diaphragm lengths measured on chest X rays from 22 normal subjects. At total lung capacity, the intersection of diaphragm and chest wall contours corresponds to the anatomic junction of diaphragm and chest wall. This point is located by skeletal landmarks to reveal the entire diaphragm contour on films taken at lower lung volumes. To validate the X-ray measurements, corresponding diameters were measured on 32 normal diaphragms at necropsy. After correction for height and diaphragm position, in vivo and necropsy length estimates along the coronal section agreed within 9%. The diaphragm length-lung volume relation is curvilinear, with length increasing primarily in the portion of the diaphragm apposed to the chest wall. As length increases, Pmus and Pdi rise sharply then plateau, generally conforming to force-length behavior of isolated muscle. However, absence of a Pdi peak at presumed diaphragm resting length suggests that Pdi is submaximal during voluntary inspiratory effort.

The dynamics of voluntary cough were studied in healthy supine subjects during four successive infusions of d-tubocurarine (dTc) (0.05 mg/kg) to assess the effects of progressive expiratory muscle weakness on cough performance. Curarization produced a progressive decline in maximal static expiratory muscle strength (PEmax) measured at the mouth and in pleural pressures (Ppl) generated during coughing. Expiratory flow rates during coughing did not decrease except during the initial cough from total lung capacity with the last dTc dose (18% below control). This was associated with a decrease in end-inspiratory volume prior to coughing and with a marked decrease in Ppl to 30% of control. Although the decrease in flow rates was minimal compared with Ppl, flow patterns suggest that dynamic airway compression was reduced during these coughs. We conclude that the principal effect of the expiratory muscle weakness in curarized subjects is to reduce the cough-induced dynamic compression and linear velocity of airflow though the major intrathoracic airways.

A single derived index of the power spectrum of the diaphragm electromyogram (EMG) has been used in detecting fatigue. Additional information in the EMG could be used to study diaphragm function in other respiratory conditions. Diaphragm EMGs and calculated power spectra at 12 frequencies were measured in normal subjects and patients with severe chronic obstructive pulmonary disease during several respiratory maneuvers both before and after treadmill exercise to dyspnea. The power spectra were characterized by the first five moments. Changes in the EMG were similar when assessed by multivariate analysis of variance of the spectral estimates or of the moments. Factor analysis provided two latent variables that correlated with the first and second moment respectively. The first moment was found to be the most sensitive single discriminant of fatigue and is only slightly improved by adding other information. It is concluded that the first and second moments of the EMG power spectra provide a concise, parsimonious description of the changes in the EMG.

Respiratory mechanics were studied in six supine conscious volunteers during progressive muscle weakness produced by infusion of d-tubocurarine. Partial curarization was carried out to the point of abolishing head lift ability and handgrip strength. At all levels of partial paralysis, expiratory muscle strength was significantly more impaired than inspiratory strength. Despite this, subjects maintained relatively normal maximal expiratory flow rates, whereas inspiratory flows decreased significantly. The diminished inspiratory flows are not fully explained by decreased driving pressures during force inspiration, since inspiratory resistance increased significantly with the decreased flow. Inspiratory flow patterns suggest a variable extrathoracic obstruction most likely due to the absence of normal airway abductor activity during inspiration. Maximal respiratory muscle weakness decreased forced vital capacity by 29% and total lung capacity by 15%. The decreased level of lung inflation did not alter lung elastic recoil. Functional residual capacity was unchanged, but inspiratory capacity decreased by 25% and residual volume increased by 38%. These changes are in accord with predictions based on the decreased muscle strength and normal respiratory system recoil.

To examine the validity of the acoustical stapedial reflex (AR) as an index of neuromuscular weakness, the AR was measured along with other indices of muscle strength during administration of d-tubocurarine (dTc) to six healthy subjects. AR decreased immediately after each dTc dose and preceded changes in handgrip strength and respiratory muscle strength, but the peak effects of each dose similarly affected AR and other muscle strength. The findings with electrocutaneous stimulation and effects on growth function of the AR indicate that dTc affects primarily stapedius muscle contraction, the efferent portion of the reflex arc, and does not affect afferent or central portions of the reflex. We therefore conclude that the AR is a valid index of the integrity of neuromuscular transmission which promptly reflects early phase weakness. Unlike other measures of muscle strength, AR testing does not depend on subject cooperation, and involves no discomfort. The test therefore provides a useful means of assessing neuromuscular weakness.

The diseases which are commonly complicated by hypercapnic respiratory failure also compromise the respiratory muscles in several ways. Increased work of breathing, mechanical disadvantage, neuromuscular disease, impaired nutritional status, shock, hypoxemia, acidosis, and deficiency of potassium, magnesium, and inorganic phosphorus are the major non-neurologic factors which contribute to respiratory muscle fatigue and failure. Respiratory muscle fatigue has two components. High frequency fatigue occurs rapidly with intense contractile efforts but is usually not severe. It also recovers rapidly with rest. Low frequency fatigue develops more slowly but is severe and requires hours for recovery. Since the spontaneous rate of neural stimulation is predominantly in the low frequency range, this component of fatigue is of particular clinical importance. Fatigue of the inspiratory muscles leads to acute respiratory acidosis, but before carbon dioxide retention occurs, it can be recognized from characteristic symptoms and signs. These include dyspnea which responds to mechanical ventilation, rapid shallow breathing, and asynchronous movements of the chest and abdomen. Inspiratory muscle fatigue must be treated by putting these muscles to rest, by mechanically supporting ventilation. In addition, underlying metabolic nutritional and circulatory abnormalities must be corrected and infection treated. Aminophylline and isoproterenol can restore inspiratory muscle contractility, but controlled clinical trials remain to be done regarding their application in acute and chronic respiratory failure. Inspiratory muscle training improves strength and endurance in patients with obstructive lung disease, cystic fibrosis, and spinal cord injury, but does not always improve physical exercise performance. Again, more work is needed to develop the indications for inspiratory muscle training and to determine the optimum type and duration of the training regimen.

We present a case of severe breathing abnormality during sleep in a young man who had had poliomyelitis 20 yr before. His sleep disorder led to respiratory failure and cor pulmonale, which were greatly improved by oxygen therapy. A study of this case and those previously described supports the notion that brainstem damage during acute poliomyelitis is important in the later appearance of sleep-disordered breathing. In addition, such patients usually have mechanical abnormalities involving the thoracic cage and respiratory muscles. These ventilatory restrictions amplify the pathophysiologic effects of abnormal central nervous system control of breathing during sleep, and we suggest that their presence has a key role in the development of sleep apnea syndrome in these patients.

We studied 53 patients with proximal myopathy to determine at what level of muscle weakness hypercapnic respiratory failure is likely, and which tests of pulmonary function or respiratory muscle strength would best suggest this development. Respiratory muscle strength was determined from maximal static efforts and in half the patients, both inspiratory and expiratory muscle strengths were less than 50% of normal. In the 37 patients without lung disease respiratory muscle weakness was accompanied by significant decreases in vital capacity, total lung capacity, and maximum voluntary ventilation; by significant increases in residual volume and arterial carbon dioxide tension (PaCO2); and greater likelihood of dependence on ventilators, atelectasis, and pneumonia. Hypercapnia was particularly likely when respiratory muscle strength was less than 30% of normal in uncomplicated myopathy, and when vital capacity was less than 55% of the predicted value in any patient.

To assess the effect of chronic debilitation on respiratory muscle function, we studied 16 poorly nourished (PN) patients without pulmonary disease, and 16 well-nourished (WN) subjects matched for age and sex. Body weight, vital capacity (VC), maximal voluntary ventilation (MVV), and maximal static inspiratory and expiratory pressures (PImax and PEmax) were measured and expressed as percent predicted. Respiratory muscle strength (RMS) was calculated as (% PImax + % PEmax)2. Body weight was 71% predicted in the PN group and 104% in the WN group. The RMS, MVV, and VC were 37%, 41%, and 63%, respectively, of the values in the WN group (p less than 0.001). The 60% reduction in RMS was shared almost equally among inspiratory and expiratory muscles, and PEmax was linearly related to body weight. Because malnutrition reduces both respiratory muscle strength and MVV, it may well impair respiratory muscle capacity to handle increased ventilatory loads in thoracopulmonary disease.

A questionnaire requesting information about complications resulting from transbronchial lung biopsy was sent to 178 directors of respiratory disease training programs in the United States and Canada. Ninety-six questionnaires (54%) were returned, listing 5,450 transbronchial lung biopsy procedures. Thirteen deaths were directly or temporally related to the procedure. Nine patients died from hemorrhage. Eight of these patients had underlying diseases or were receiving drugs known to affect hemostasis. One also had pulmonary hypertension. One patient died from a tension pneumothorax that rapidly progressed more than two hours after the procedure. Analysis of the exact data, which were available for 2,628 procedures, indicated that pneumothorax, hemorrhage exceeding 50 ml, and death occurred in 5.5, 1.3, and 0.20% of procedures, respectively.