Friday, February 13, 2015

Lung hemorrhage, pulmonary edema, and alveolitis

Among adults, pills constitute 7% of all foreign-body aspiration. A symptom triad of cough, wheezing, and decreased air entry should alert clinicians to suspect aspiration. The presence of the foreign object in the airway may lead to airway obstruction, atelectasis, granulation tissue formation, postobstructive pneumonia, and bronchiectasis. All aspirated foreign bodies require immediate attention.

Sucralfate is an oral cytoprotective agent used to treat and prevent gastroduodenal ulcers. Sucralfate demonstrates a high affinity for erosive mucosa, due to its viscous adhesiveness and formation of polyvalent bridges. It also buffers acid, inhibits the action of pepsin, and absorbs bile salts. Furthermore, sucralfate binds to uninjured mucosa and acts as a barrier on regenerated and normal mucosa. Aspiration of sucralfate has been reported to cause acute hypoxemia from complete occlusion of a lobar bronchus.
Lung hemorrhage
Lung hemorrhage

The sucralfate tablet can rapidly expand when in contact with bronchial mucosa. A large, moist, sucralfate tablet can completely occlude a bronchus, causing acute respiratory failure. In animal models, sucralfate suspension has also been shown to cause lung hemorrhage, pulmonary edema, and alveolitis. In patients at risk for aspiration, the use of sucralfate granules instead of its tablet form is recommended.

Capsule endoscopy is a widely accepted imaging modality with a good diagnostic yield and good safety profile. The most common complication is capsule retention, reported in about 1% to 2% of procedures. Capsule aspiration in the airways is rarer yet and is a potentially fatal complication in the presence of chronic lung diseases. This condition commonly occurs in elderly patients with or without prior history of swallowing disorders. 

It may result in hypoxemic respiratory failure, obstructive pneumonitis, and bronchial injury during its removal. In elderly patients who have difficulty swallowing, the capsule might need to be placed in the duodenum endoscopically to prevent its aspiration. Regardless, the aspirated endoscopic capsule should be retrieved immediately.

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Thursday, February 12, 2015

Canadian HealthCare: Smooth muscle hyperplasia

Imatinib is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia by inhibiting BCR-ABL kinase activity. It can also block other factors, such as c-kit ligand, stem cell factor, and platelet-derived growth factor (PDGF) receptor tyrosine kinase activity. It was reported to block the increase of ASM mass in a mouse asthma model.
Smooth muscle hyperplasia
Smooth muscle hyperplasia

PDGF receptor is a receptor tyrosine kinase. Its signaling, known as a cell migration inducer, also causes ASMC proliferation. Hirota et al showed its plausibility as an agent of remodeling by demonstrating an increase of ASM mass and cellular proliferation using an adenovirus-mediated PDGF overexpression mouse asthma model.

TGF-b is a pleiotropic cytokine, which was reported to increase in the asthmatic airways. Its expression can be detected in both immune cells and structural cells. In a COPD mouse model, Podowski et al showed the improvement of subepithelial collagen deposition and airway wall thickening by inhibition of TGF-b.

Eotaxin (CCL) is a chemokine that is known for its potent chemoattractant effect for eosinophils. Using a mouse model, Wegmann et al reported that antagonizing CCR, an eotaxin receptor, prevented some features of airway remodeling, goblet metaplasia, subepithelial fibrosis, and increase of number of myofibroblasts.

Based on the pathologic findings, the cellular events occurring in airway remodeling are smooth muscle hyperplasia and hypertrophy, epithelial cell hyperplasia and goblet cell metaplasia, subepithelial fibrosis, and neovascularization. Smooth muscle hyperplasia is inferred by the increase of their proliferation and migration. Asthmatic ASMCs in culture retain the property of more rapid proliferation rates compared with normal ASMC. ASMC migration toward the airway epithelium has been suggested from the findings on proximal asthmatic airway bronchial biopsy samples. It is postulated that ASMC migration may be a contributor to the expansion of smooth muscle bundles.

Physiologic scales and symptoms have been used to assess the clinical states of patients with asthma. Given the fact that asthma and COPD are inflammatory syndromes and complexes of several phenotypes that cause reversible or partial airway narrowing, more detailed classification of the patients and appropriate therapies for each group are necessary. For example, treatment strategies based on monitoring sputum eosinophil counts reduce asthma exacerbations. However, we are lacking specific biomarkers that reflect airway remodeling.

Diagnosis of ARDS or ALI was made according to criteria of the American-European Consensus Conference on ARDS

This prospective, observational study was carried out on 29 patients (24 men and 5 women; median age, 50 years; range, 19 to 70 years): 19 patients with ARDS and 10 patients with ALI. Diagnosis of ARDS or ALI was made according to criteria of the American-European Consensus Conference on ARDS (acute onset of respiratory failure, bilateral infiltrates on chest radiography, pulmonary-artery wedge pressure < 18 mm Hg or the absence of clinical evidence of left atrial hypertension; ALI was considered to be present if Pao2/Flo2 ratio was < 300, and ARDS if Pao2/Flo2 ratio was < 200). ALI/ARDS was observed after major surgery, multiple trauma, head injury, thorax trauma, pancreatitis, pneumonia, or severe sepsis. Exclusion criteria for enrollment of patients were hemofiltration, massive transfusion in the immediately preceding 24 h, medical history of chronic lung disease, and immunosuppressive therapy. 
Diagnosis of ARDS
Diagnosis of ARDS

All patients were receiving mechanical ventilation and standard intensive care support. Severity of illness was scored during the first 24 h after onset of ALI/ARDS using the simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA). For calculation of the SAPS II and SOFA score, which were single determinations during the first day after onset of ALI/ARDS, the worst values of physiologic and clinical variables observed over 24 h were taken in account as originally described. 

BAL (routine protocol for microbiologic culture with 100 mL of 0.9% saline solution sequentially instilled and suctioned in 20-mL portions) was performed in a subsegment of the right middle lobe of lung within 12 h and 24 h after onset of ALI/ARDS. Blood for determination of G-CSF, ENA-78, and IL-8 in serum was obtained from the patients at the same time. The protocol for this study was approved by the Ethics Committee of the Leopold-Franzens-University of Innsbruck.

Recovered BALF volume was not different between the ARDS and ALI groups (ARDS group, 43 mL [range, 28 to 57 mL]; ALI group, 41.5 mL [range, 30 to 56 mL]; p = 0.5819). After collecting BALF in tubes, the fluid retrieved was filtered through sterile gauze and centrifuged at 300g at 4°C for 10 min to remove mucus and cells. The supernatants were aliquoted into cups and frozen at — 80°C until analysis. Blood sampling was performed with three 4-mL syringes and then ice cooled. Blood was allowed to clot and then centrifuged at 1,000g for 10 min at 4°C. Multiple aliquots of serum were frozen at — 80°C until analysis.

Extent of Lung Fibrosis on HRCT

There were 11 deaths (42%) in the fibrotic group and 1 death (2%) in the nonfibrotic group during the median follow-up period of 5.8 years (Fig 1). In the regression analysis, the presence of HRCT fibrosis, more severe impairment of pulmonary function parameters, and presence of crackles on auscultation were predictive of reduced survival (p < 0.05 for all) [Table 2]. The age-adjusted hazard ratio for mortality in patients with HRCT fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p < 0.0001). The presence of honeycombing in itself was not predictive of mortality (only five patients had honeycombing).
Lung Fibrosis
Lung Fibrosis

Figure 3 demonstrates the relationship between the fibrosis extent and mortality. Mortality was highest in patients with > 40% of lung involvement (5 of 6 patients died, 83%), followed by those with 10 to 40% involvement (3 of 6 patients died, 50%), followed by those with < 10% involvement (3 of 14 patients died, 21%) and those with no lung fibrosis (1 of 43 patients died, 2%).

Extent of Lung Fibrosis on HRCT

Figure 3. Relationship between the fibrosis extent and mortality. The presence of fibrosis was assessed semiquantitatively as absent or as involving < 10%, 10 to 40%, or > 40% of the lung. The numbers in the bar graph refer to the fraction of deceased patients in each category (nominator) over the number of all patients in that category (denominator).


Our study found radiologic evidence of parenchymal fibrosis to be associated with decreased survival in patients with HP. Furthermore, the extent of parenchymal fibrosis, as assessed by semiquantitative visual scoring of CT, correlated with mortality.

HP may lead to progressive clinical deterioration and death in a proportion of patients. Mortality in our study was 17%, comparable to reports from other tertiary care referral medical centers. The long-term mortality estimates in chronic HP are reported as low as 1% in the community study, of patients with farmers’ lung, and as high as 27% in the population of patients from tertiary referral medical centers. A large-scale epidemiologic study from England suggests that all-cause mortality is three times higher in patients with HP compared to the general population.

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Wednesday, February 11, 2015

Health Care Mall: Dyspnea

The same descriptors of dyspnea are associated with different diseases, suggesting that these aspects of breathlessness may be shared by similar receptors or neural pathways. (3) Certain diseases are associated with a unique set of descriptors of breathlessness that likely relate to different pathophysiologic mechanisms. (4) The majority of patients report that dyspnea occurs during inspiration, thus implicating the role of the respiratory muscles in the experience of breathlessness. 
 (5) Ethnic and cultural differences are reflected in the words or phrases used by patients to describe dyspnea. (6) Patients differentiate between sensory (intensity) and affective (unpleasant) qualities of breathlessness. (7) Descriptors of dyspnea are related to the intensity level of breathlessness. (8) Patients throughout the world with COPD report similar descriptors of breath-lessness.

In the present issue of CHCM Pharmacy, Williams and colleagues prospectively evaluated whether descriptors of dyspnea can differentiate between patients with COPD and age-matched healthy individuals. Initially, subjects volunteered relevant words or phrases and then endorsed (selected) up to three statements from the aggregate list to describe “when their breathing was uncomfortable.” Cluster analysis showed that “volunteered” and up to three “endorsed” descriptors of dyspnea could be used to categorize a majority of subjects into their original group classification (COPD or healthy individuals).

In general, only patients with COPD, but not healthy individuals, volunteered affective words such as “frightening,” “worried,” “helpless,” “depressed,” and “awful” to describe their breathing difficulty. These expressions were not included in the list of 15 descriptors used for selection; the phrases in the list include only somatic descriptors of breathlessness (eg, “hard to breathe” and “chest tightness”). Williams and colleagues proposed that these affective descriptions are intended to convey the threat perceived by the patients to their breathing difficulty. These experiences are consistent with the statement by Comroe that “dyspnea. . . involves both perception of the sensation by the patient and his reaction to the sensation.”

Tuesday, February 10, 2015

Time To Start Comparing Apples With Apples

The study by Williams and colleagues advances the field by demonstrating that specific descriptors of breathlessness can be used to suggest a diagnosis of COPD. Prospective testing is necessary to examine whether fluency in this language can differentiate other common respiratory diseases. In a preliminary study of 142 patients presenting with a chief complaint of breathlessness, Harver and associates found that the descriptor “chest tightness or constriction” had a specificity of 95% and positive predictive value of 86% for the diagnosis of asthma. Two phrases “effort or work of breathing” and “can’t get a deep breath” had a sensitivity of 74% for the diagnosis of COPD.
health-care technologies
health-care technologies

Based on this information, we encourage physicians and other health-care providers to ask patients about descriptors of dyspnea as part of the medical history. In the office setting, the nurse could take vital signs and then ask each patient to describe “what it feels like” when he/she has breathing discomfort. The nurse could write down (or enter into a computer) the key words along with the vital signs. The nurse could then give each patient a list of descriptors and ask him/her to select the “best two or three” that describe breathlessness. It is time for physicians to become fluent in the language of dyspnea! This will help us to better understand the experience of our patients, to diagnose the cause of breathlessness in a patient, and to and enhance our therapeutic efforts to provide relief.

She introduction of health-care technologies into medical practice is happening at a breathtaking pace. Some of these technologies are real advances and provide great benefits to patients, but many others offer only slight improvements despite substantially increasing health-care costs. Unfortunately, when faced with a decision to implement new technologies in their practices, many practitioners are often at a loss in determining the relative strengths and weaknesses of their options. When perusing the literature on reports about new technologies, it is frequently only case series or studies aimed at obtaining Food and Drug Administration approval that one can find, but no proper comparisons with conventional and established approaches.