#Las personas que comen muchas #grasas saturadas tienen más riesgo de desarrollar #cáncer de pulmón (J Clin Oncol)

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Una dieta saludable también puede ayudar a reducir el riesgo de neoplasias malignas de los pulmones.

Una dieta saludable también puede ayudar a reducir el riesgo de neoplasias malignas de los pulmones.

Las personas que comen muchas grasas saturadas tienen más riesgo de desarrollar cáncer de pulmón que aquellas que siguen una dieta baja en grasas, según ha puesto de manifiesto un estudio llevado a cabo por investigadores de la University Medical Center en Nashville (Estados Unidos).

Para alcanzar esta conclusión, publicada en “Journal of Clinical Oncology”, los investigadores examinaron datos de 10 estudios publicados previamente en los Estados Unidos, Europa y Asia, que analizaron cómo la ingesta de grasas en la dieta influye en las probabilidades de neoplasias malignas de los pulmones.

En conjunto, los estudios más pequeños tuvieron más de 1,4 millones de participantes, incluyendo 18.822 con casos de cáncer de pulmón identificados durante un seguimiento promedio de más de nueve años.

Con ello, los científicos les clasificaron en cinco categorías, desde el más bajo hasta el más alto consumo de grasas totales y saturadas. También les analizaron según las cantidades más bajas hasta las más altas de grasas insaturadas dietéticas ingeridas.

En general, las personas que comieron la mayoría de las grasas no saturadas tuvieron un 8% menos probabilidades de desarrollar cáncer de pulmón que las personas que comieron menos cantidades.

Además, los investigadores observaron que cuando se sustituían en un 5% las calorías de las grasas saturadas por las insaturadas, se producía un 16% menos de riesgo de cáncer de pulmón de células pequeñas y un 17% menos de carcinoma de células escamosas.

“Mientras que la mejor manera de reducir el riesgo de cáncer de pulmón es no fumar, una dieta saludable también puede ayudar a reducir el riesgo de cáncer de pulmón. Específicamente, nuestros hallazgos sugieren que la reducción de la ingesta de grasas saturadas, especialmente entre los fumadores y fumadores recientes, puede ayudar a prevenir no sólo las enfermedades cardiovasculares, sino también el cáncer de pulmón”, han zanjado los expertos.

#Tuberculosis Treatment & Management

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Author: Thomas E Herchline, MD; Chief Editor: Michael Stuart Bronze, MD  more…

Anteroposterior chest radiograph of a young patient who presented to the emergency department (ED) with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine (

Practice Essentials
Tuberculosis (TB) (see the image below), a multisystemic disease with myriad presentations and manifestations, is the most common cause of infectious disease–related mortality worldwide. Although TB rates are decreasing in the United States, the disease is becoming more common in many parts of the world. In addition, the prevalence of drug-resistant TB is increasing worldwide.

Anteroposterior chest radiograph of a young patient who presented to the emergency department (ED) with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine (
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See 11 Travel Diseases to Consider Before and After the Trip, a Critical Images slideshow, to help identify and manage infectious travel diseases.

Signs and symptoms

Classic clinical features associated with active pulmonary TB are as follows (elderly individuals with TB may not display typical signs and symptoms):
Weight loss/anorexia
Night sweats
Chest pain (can also result from tuberculous acute pericarditis)
Symptoms of tuberculous meningitis may include the following:
Headache that has been either intermittent or persistent for 2-3 weeks
Subtle mental status changes that may progress to coma over a period of days to weeks
Low-grade or absent fever
Symptoms of skeletal TB may include the following:
Back pain or stiffness
Lower-extremity paralysis, in as many as half of patients with undiagnosed Pott disease
Tuberculous arthritis, usually involving only 1 joint (most often the hip or knee, followed by the ankle, elbow, wrist, and shoulder)

Symptoms of genitourinary TB may include the following:
Flank pain
Frequent urination
In men, a painful scrotal mass, prostatitis, orchitis, or epididymitis
In women, symptoms mimicking pelvic inflammatory disease
Symptoms of gastrointestinal TB are referable to the infected site and may include the following:
Nonhealing ulcers of the mouth or anus
Difficulty swallowing (with esophageal disease)
Abdominal pain mimicking peptic ulcer disease (with gastric or duodenal infection)
Malabsorption (with infection of the small intestine)
Pain, diarrhea, or hematochezia (with infection of the colon)
Physical examination findings associated with TB depend on the organs involved. Patients with pulmonary TB may have the following:
Abnormal breath sounds, especially over the upper lobes or involved areas
Rales or bronchial breath signs, indicating lung consolidation
Signs of extrapulmonary TB differ according to the tissues involved and may include the following:
Neurologic deficit
Cutaneous lesions
The absence of any significant physical findings does not exclude active TB. Classic symptoms are often absent in high-risk patients, particularly those who are immunocompromised or elderly.
See Clinical Presentation for more detail.


Screening methods for TB include the following:
Mantoux tuberculin skin test with purified protein derivative (PPD) for active or latent infection (primary method)
In vitro blood test based on interferon gamma release assay (IGRA) with antigens specific for Mycobacterium tuberculosis for latent infection
Obtain the following laboratory tests for patients with suspected TB:
Acid-fast bacilli (AFB) smear and culture using sputum obtained from the patient: Absence of a positive smear result does not exclude active TB infection; AFB culture is the most specific test for TB
HIV serology in all patients with TB and unknown HIV status: Individuals infected with HIV are at increased risk for TB
Other diagnostic testing may warrant consideration, including the following:
Specific enzyme-linked immunospot (ELISpot)
Nucleic acid amplification tests
Blood culture
Positive cultures should be followed by drug susceptibility testing; symptoms and radiographic findings do not differentiate multidrug-resistant TB (MDR-TB) from fully susceptible TB. Such testing may include the following:
Direct DNA sequencing analysis
Automated molecular testing
Microscopic-observation drug susceptibility (MODS) and thin-layer agar (TLA) assays
Additional rapid tests (eg, BACTEC-460, ligase chain reaction, luciferase reporter assays, FASTPlaque TB-RIF)
Obtain a chest radiograph to evaluate for possible associated pulmonary findings. The following patterns may be seen:
Cavity formation: Indicates advanced infection; associated with a high bacterial load
Noncalcified round infiltrates: May be confused with lung carcinoma
Homogeneously calcified nodules (usually 5-20 mm): Tuberculomas, representing old infection
Primary TB: Typically, pneumonialike picture of infiltrative process in middle or lower lung regions
Reactivation TB: Pulmonary lesions in posterior segment of right upper lobe, apicoposterior segment of left upper lobe, and apical segments of lower lobes
TB associated with HIV disease: Frequently atypical lesions or normal chest radiographic findings
Healed and latent TB: Dense pulmonary nodules in hilar or upper lobes; smaller nodules in upper lobes
Miliary TB: Numerous small, nodular lesions that resemble millet seeds
Pleural TB: Empyema may be present, with associated pleural effusions
Workup considerations for extrapulmonary TB include the following:
Biopsy of bone marrow, liver, or blood cultures
If tuberculous meningitis or tuberculoma is suspected, perform lumbar puncture
If vertebral ( Pott disease) or brain involvement is suspected, CT or MRI is necessary
If genitourinary complaints are reported, urinalysis and urine cultures can be obtained
See Workup for more detail.


Physical measures (if possible or practical) include the following:
Isolate patients with possible TB in a private room with negative pressure
Have medical staff wear high-efficiency disposable masks sufficient to filter the bacillus
Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 weeks of treatment)
Initial empiric pharmacologic therapy consists of the following 4-drug regimens:
Either ethambutol or streptomycin [1]
Special considerations for drug therapy in pregnant women include the following:
In the United States, pyrazinamide is reserved for women with suspected MDR-TB
Streptomycin should not be used
Preventive treatment is recommended during pregnancy
Pregnant women are at increased risk for isoniazid-induced hepatotoxicity
Breastfeeding can be continued during preventive therapy
Special considerations for drug therapy in children include the following:
Most children with TB can be treated with isoniazid and rifampin for 6 months, along with pyrazinamide for the first 2 months if the culture from the source case is fully susceptible.
For postnatal TB, the treatment duration may be increased to 9 or 12 months
Ethambutol is often avoided in young children
Special considerations for drug therapy in HIV-infected patients include the following:
Dose adjustments may be necessary [2, 3]
Rifampin must be avoided in patients receiving protease inhibitors; rifabutin may be substituted
Considerations in patients receiving antiretroviral therapy include the following:
Patients with HIV and TB may develop a paradoxical response when starting antiretroviral therapy
Starting antiretroviral therapy early (eg, < 4 weeks after the start of TB treatment) may reduce progression to AIDS and death [4]
In patients with higher CD4+ T-cell counts, it may be reasonable to defer antiretroviral therapy until the continuation phase of TB treatment [5]
Multidrug-resistant TB
When MDR-TB is suspected, start treatment empirically before culture results become available, then modify the regimen as necessary. Never add a single new drug to a failing regimen. Administer at least 3 (preferably 4-5) of the following medications, according to drug susceptibilities:
An aminoglycoside: Streptomycin, amikacin, capreomycin, kanamycin
A fluoroquinolone: Levofloxacin (best suited over the long term), ciprofloxacin, ofloxacin
A thioamide: Ethionamide, prothionamide
Para-aminosalicylic acid
Rifabutin as a substitute for rifampin
A diarylquinoline: Bedaquiline
Surgical resection is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Procedures include the following:
Segmentectomy (rarely used)
Pleurectomy for thick pleural peel (rarely indicated)
Latent TB
Recommended regimens for isoniazid and rifampin for latent TB have been published by the US Centers for Disease Control and Prevention (CDC) [6] : An alternative regimen for latent TB is isoniazid plus rifapentine as directly observed therapy (DOT) once-weekly for 12 weeks [7, 8] ; it is not recommended for children under 2 years, pregnant women or women planning to become pregnant, or patients with TB infection presumed to result from exposure to a person with TB that is resistant to 1 of the 2 drugs.

Approach Considerations
Isolate patients with possible tuberculosis (TB) infection in a private room with negative pressure (air exhausted to outside or through a high-efficiency particulate air filter). Medical staff must wear high-efficiency disposable masks sufficient to filter the tubercle bacillus. Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 wk of treatment). Unfortunately, these measures are neither possible nor practical in countries where TB is a public health problem.
Drug therapy

For initial empiric treatment of TB, start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the TB isolate is known to be fully susceptible, ethambutol (or streptomycin, if it is used as a fourth drug) can be discontinued. [1]
Patients with TB who are receiving pyrazinamide should undergo baseline and periodic serum uric acid assessments, and patients with TB who are receiving long-term ethambutol therapy should undergo baseline and periodic visual acuity and red-green color perception testing. The latter can be performed with a standard test, such as the Ishihara test for color blindness.
After 2 months of therapy (for a fully susceptible isolate), pyrazinamide can be stopped. Isoniazid plus rifampin are continued as daily or intermittent therapy for 4 more months. If isolated isoniazid resistance is documented, discontinue isoniazid and continue treatment with rifampin, pyrazinamide, and ethambutol for the entire 6 months. Therapy must be extended if the patient has cavitary disease and remains culture-positive after 2 months of treatment.
Directly observed therapy (DOT) is recommended for all patients. With DOT, patients on the above regimens can be switched to 2- to 3-times per week dosing after an initial 2 weeks of daily dosing. Patients on twice-weekly dosing must not miss any doses. Prescribe daily therapy for patients on self-administered medication.

Patients diagnosed with active TB should undergo sputum analysis for Mycobacterium tuberculosis weekly until sputum conversion is documented. Monitoring for toxicity includes baseline and periodic liver enzymes, complete blood cell (CBC) count, and serum creatinine.

Treatment in Children
Most children with TB can be treated with isoniazid and rifampin for 6 months, along with pyrazinamide for the first 2 months if the culture from the source case is fully susceptible.
For postnatal TB, many experts increase the treatment duration to 9 or 12 months because of the possible impaired immune system in children younger than 12 months. Bacillus Calmette-Guérin (BCG) vaccine is not recommended in infants in the United States but is commonly used around the world.
Isoniazid tablets may be crushed and added to food. Isoniazid liquid without sorbitol should be used to avoid osmotic diarrhea, which can cause decreased absorption.
Rifampin capsules may be opened and the powder added to food. If rifampin is not tolerated, it may be taken in divided doses 20 minutes after light meals.
Ethambutol is often avoided in young children because of difficulties monitoring visual acuity and color perception. However, studies show that ethambutol (15 mg/kg) is well tolerated and can prevent further resistance if the child is infected with a resistant strain. Go to Pediatric Tuberculosis for complete information on treatment of children.

Treatment in HIV-Infected Patients
Treatment regimens for active or latent TB in patients with HIV infection are similar to those used in HIV-negative patients, but dose adjustments may be necessary. [2, 3] The most significant differences involve the avoidance of rifampin in patients who are on protease inhibitors. Rifabutin may be used in place of rifampin in such patients.
Antiretroviral therapy

Patients with HIV and TB may develop a paradoxical response (immune reconstitution inflammatory syndrome [IRIS]) when starting antiretroviral therapy. This response has been attributed to a stronger immune response to M tuberculosis. Clinical findings include fever, worsening pulmonary infiltrates, and lymphadenopathy.
However, in an open-label, randomized trial, Abdool Karim et al concluded that the initiation of antiretroviral therapy during TB therapy significantly improved patient survival. In this study, the mortality rate with simultaneous initiation of antiretroviral therapy and TB therapy was 5.4 deaths per 100 person-years (25 deaths in 429 patients), compared with 12.1 deaths per 100 person-years (27 deaths in 213 patients) with antiretroviral therapy started after the completion of TB therapy, a relative reduction of 56%. [4]
Subsequent studies by these and other researchers found that starting antiretroviral therapy early (eg, within 4 weeks after the start of TB treatment) reduced progression to AIDS and death. In patients with higher CD4+ T-cell counts, however, deferring initiation of antiretroviral therapy until the continuation phase of TB treatment may be a reasonable strategy, because the risks of IRIS and of adverse events that necessitate switching of antiretroviral drugs are lower with later initiation of antiretroviral therapy. [5]
Treatment length and recurrence rate

Swaminathan et al reported a significantly lower bacteriologic recurrence rate with 9 months, instead of 6 months, of an intermittent (3 times/wk) 4-drug regimen in patients with HIV infection and newly diagnosed TB. Mortality was similar in both groups. The rate of acquired rifampin resistance was high in both groups and was not altered by the longer TB treatment. [2]
Tuberculous meningitis

In patients with tuberculous meningitis, dexamethasone added to routine 4-drug therapy reduces complications.

Treatment of Multidrug-Resistant TB
When MDR-TB is suspected, because of a relevant history or epidemiologic information, treatment is initiated after sputum specimens are drawn for culture and sensitivity testing; however, treatment must be started empirically before culture results become available. Once results are known, the regimen is modified according to susceptibilities. (Costs are many times higher for the treatment of MDR-TB.)
The complexity of MDR-TB treatment lies in the futility of using isoniazid and rifampin. Isoniazid has the strongest antibactericidal action and significantly contributes to making patients rapidly noninfectious; rifampin has unique antibacterial properties against dormant bacilli that are no longer in the active phase of replication.
When initiating treatment, utilize at least 3-5 previously unused drugs for which there is in vitro susceptibility. Levofloxacin, which is a fluoroquinolone, has been shown to be best suited long-term and should be included in the regimen.
Never add a single new drug to a failing regimen. Administer at least 3 (preferably 4-5) of the following medications, according to drug susceptibilities:
An aminoglycoside – Ie, streptomycin, amikacin, capreomycin, kanamycin
A fluoroquinolone – Ie, levofloxacin, ciprofloxacin, ofloxacin
A thioamide – Eg, ethionamide, prothionamide
Para-aminosalicylic acid
A diarylquinoline: Bedaquiline
Consider rifabutin as a substitute for rifampin, as approximately 15% of rifampin-resistant strains are rifabutin sensitive.
Successful MDR-TB treatment is more likely in association with such factors as lower prior patient exposure to anti-TB drugs, a higher number of anti-TB drugs to which the infection is still susceptible, and a shorter time since the first TB diagnosis (indicating less advanced disease).
Continue treatment for MDR-TB for 18-24 months after sputum culture conversion. The drugs should be prescribed daily (no intermittent therapy), and the patient should always be on DOT. Weekend DOT may not be possible; therefore, giving self-administered oral drugs on Saturdays and Sundays may be reasonable. All patients should be closely observed for 2 years after completion of treatment, with a low threshold for referral to TB centers.
Novel drugs for TB are currently under development and may prove valuable for treatment of MDR-TB. The diarylquinoline antimycobacterial, bedaquiline (Sirturo), was approved by the FDA in December 2012 as part of a 22-week multidrug regimen for pulmonary MDR-TB. Approval was based on phase 2 data that showed bedaquiline significantly improved time to sputum culture conversion and included 2 consecutive negative sputum cultures collected at least 25 days apart during treatment. At week 24, sputum culture conversion was observed in 77.6% of patients in the bedaquiline treatment group compared with 57.6% of patients in the placebo treatment group (p = 0.014). [73, 74]

In another phase II study by Diacon et al, bedaquiline (TMC207) added to standard therapy for MDR-TB reduced the time to conversion to a negative sputum culture compared with placebo and increased the proportion of patients with conversion of sputum culture (48% vs 9%). [75]
Provisional guidelines from the Centers for Disease Control and Prevention (CDC) include use of bedaquiline for FDA-approved and off-label uses. In addition to the approved indication as part of at least a 4-drug regimen for treatment multidrug-resistant tuberculosis, the guidelines include use on a case-by-case basis for children, HIV-infected persons, pregnant women, persons with extrapulmonary MDR TB, and patients with comorbid conditions on concomitant medications when an effective treatment regimen cannot otherwise be provided. [76, 77]
The diagnosis of extensively drug-resistant TB (XDR-TB) is established with an isolate that is resistant to isoniazid, rifampin, at least 1 of the quinolones, and at least 1 injectable drug. Treatment options for XDR-TB are very limited, and XDR-TB carries a very high mortality rate.
A CDC analysis of the prevalence, trends, and risk factors for initial resistance to pyrazinamide in Mycobacterium tuberculosis complex (MTBC) cases in the United States showed that such resistance increased from 2% in 1999 to 3.3% in 2009. Pyrazinamide monoresistance was associated with younger age, Hispanic ethnicity, HIV infection, extrapulmonary disease, and normal chest radiograph and inversely associated with Asian and Black race, substance use, homelessness, and residence in a correctional facility. [78, 79]
In the same CDC analysis, pyrazinamide polyresistance was associated with Hispanic ethnicity, Asian race, previous TB diagnosis, and normal chest x-ray and inversely associated with age 45 years and older. Pyrazinamide resistance in multidrug-resistant cases was associated with female sex and previous TB diagnosis. Bacterial lineage, rather than host characteristics, was the primary predictor of pyrazinamide resistance ijn M tuberculosis cases. [78, 79]
Surgical resection

Surgical resection of an infected lung may be considered to reduce the bacillary burden in patients with MDR-TB. Surgery is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Surgery can be performed with a low mortality rate (< 3%), with prolonged periods of a chemotherapeutic regimen used for more than 1 year after surgery.
Procedures include segmentectomy (rarely used), lobectomy, and pneumonectomy. Pleurectomies for thick pleural peel are rarely indicated.
Intraoperative infection of uninvolved lung tissue has been observed in resections. Complications include the usual perioperative complications, recurrent disease, and bronchopleural fistulas.

Prevention and Consultations
The BCG vaccine continues to be used throughout much of the world and usually provides protection until early childhood. Immunity begins to wane, however, as early as 3 months after administration. [82] As previously noted, use of the BCG vaccine is not recommended in infants in the United States.
In a meta-analysis of eight randomized controlled studies involving a total of 10,320 patients aged 15 years or younger, Ayieko et al found that isoniazid prophylaxis reduced the risk of developing TB, with a pooled risk ratio (RR) of 0.65 (P  = 0.004). However, isoniazid had no effect in children who initiated treatment at 4 months of age or earlier. When those patients were excluded, isoniazid prophylaxis reduced the risk of developing TB by 59% (RR, 0.41; P < 0.001). [83]
The public health sector should be notified and involved in cases of TB. Local county health departments are expert and funded in the care of TB infection. Consultation with a primary care, pulmonology, internal medicine, or infectious disease specialist prior to initiating therapy is helpful, and it may be appropriate for this consultant to manage the antituberculous chemotherapy. Consult an expert on MDR-TB in cases of multidrug resistance.

*Extracts from Medscape

Cigarros eletrónicos são tão perigosos como os tradicionais

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Cigarros eletrónicos são tão perigosos como os tradicionais

Resultado de imagem para cigarros electronicos

Investigadores da Universidade de Connecticut, nos Estados Unidos, fizeram testes e concluíram que os danos no ADN, a informação genética das células, são idênticos aos do fumo do tabaco

Os cigarros eletrónicos são potencialmente tão perigosos para a saúde como os cigarros tradicionais. Esta é a conclusão de um estudo realizado por investigadores da Universidade de Connecticut, nos Estados Unidos, e publicado hoje na revista científica ACS Sensors.

“Os resultados do nosso estudo levam-nos a concluir que os cigarros eletrónicos tem tanto potencial para causar no ADN [informação genética] como os cigarros tradicionais sem filtro”, afirmou Karteek Kadimisetty, químico e o principal autor do estudo.

Esta conclusão vem contrariar a visão de os cigarros eletrónicos são menos tóxicos e perigosos do que o o fumo do tabaco tradicional, o que contribuiu para que se tornassem bastante populares na última década.
Os investigadores da Universidade de Connecticut testaram o vapor dos cigarros eletrónicos, com e sem nicotina, em culturas de células humanas e verificaram que não há diferenças em relação aos cigarros tradicionais no que respeita aos efeitos na molécula de ADN nas células. Ambos causam igualmente mutações no ADN.

Mesmo sem a presença de nicotina, “há centenas de químicos nos cigarros eletrónicos que podem contribuir para os danos que observamos no ADN”, sublinha Karteek Kadimisetty.

Diario de Notícias

#Diagnosis and Management of Asthma in Adults

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Diagnosis and Management of Asthma in Adults

Resultado de imagem para asthma in adults
A Review
Jennifer L. McCracken, MD1; Sreenivas P. Veeranki, MBBS, DrPH2; Bill T. Ameredes, MS, PhD3; et al William J. Calhoun, MD1,3
Author Affiliations Article Information
JAMA. 2017;318(3):279-290. doi:10.1001/jama.2017.8372

How to Diagnose and Manage Adult Asthma
Importance  Asthma affects about 7.5% of the adult population. Evidence-based diagnosis, monitoring, and treatment can improve functioning and quality of life in adult patients with asthma.

Observations  Asthma is a heterogeneous clinical syndrome primarily affecting the lower respiratory tract, characterized by episodic or persistent symptoms of wheezing, dyspnea, and cough. The diagnosis of asthma requires these symptoms and demonstration of reversible airway obstruction using spirometry. Identifying clinically important allergen sensitivities is useful. Inhaled short-acting β2-agonists provide rapid relief of acute symptoms, but maintenance with daily inhaled corticosteroids is the standard of care for persistent asthma. Combination therapy, including inhaled corticosteroids and long-acting β2-agonists, is effective in patients for whom inhaled corticosteroids alone are insufficient. The use of inhaled long-acting β2-agonists alone is not appropriate. Other controller approaches include long-acting muscarinic antagonists (eg, tiotropium), and biological agents directed against proteins involved in the pathogenesis of asthma (eg, omalizumab, mepolizumab, reslizumab).

Conclusions and Relevance  Asthma is characterized by variable airway obstruction, airway hyperresponsiveness, and airway inflammation. Management of persistent asthma requires avoidance of aggravating environmental factors, use of short-acting β2-agonists for rapid relief of symptoms, and daily use of inhaled corticosteroids. Other controller medications, such as long-acting bronchodilators and biologics, may be required in moderate and severe asthma. Patients with severe asthma generally benefit from consultation with an asthma specialist for consideration of additional treatment, including injectable biologic agents.

Asthma affects about 7.5% of adults in the United States, resulting in 1.8 million hospitalizations and 10.5 million physician office visits per year (Table 1). Asthma is more common in black (8.7%) and Puerto Rican Hispanic (13.3%) individuals than in white individuals (7.6%) and is associated with higher mortality in blacks than in whites (25.4 vs 8.8 per million annually) (Table 1). Inhaled corticosteroids increase the number of days without symptoms (by 7-21 d/mo), improve lung function (forced expiratory volume in first second of expiration [FEV1]) by 13% and peak flow by 23 to 41 L/min, and reduce symptoms of dyspnea, cough, and nighttime awakening.

Asthma exhibits considerable clinical and molecular heterogeneity (eg, atopic vs nonatopic, aspirin-exacerbated respiratory disease, obesity-associated asthma), which complicates diagnostic evaluations and affects therapeutic responsiveness. For example, patients with asthma who smoke have relative resistance to inhaled corticosteroids. Patients with asthma uncontrolled by standard treatment and with peripheral blood eosinophilia may benefit from mepolizumab or reslizumab, and those with elevated perennial allergen-specific IgE could be candidates for omalizumab. Clinical history, spirometry, and assessment of allergic sensitivities are important for diagnosis of asthma.

This review presents an evidence-based approach to the diagnosis and management of mild to moderate stable asthma in adults. For patients with severe disease, generally manifested as continuing symptoms and airway obstruction despite appropriate therapy, consultation with an asthma specialist (allergist or pulmonologist) should be sought.

The Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, Population Information Online, PubMed, and Web of Science were searched for the period from the inception of each database through March 2017 for randomized clinical trials, systematic reviews, and/or meta-analyses and for observational studies using asthma or anti-asthmatic drugs or asthma management or therapeutic as primary search terms. Titles and abstracts of the articles were initially screened, and selected articles underwent full review. The bibliographies of selected articles were manually screened for additional relevant articles. All authors agreed on the final bibliography. Emphasis was given to randomized clinical trials and articles that included information of interest to a general medical readership.

Clinical Presentation
Asthma is a heterogeneous clinical syndrome affecting the lower respiratory tract. It presents as episodic or persistent symptoms of wheezing, dyspnea, air hunger, and cough. Symptoms may be precipitated or exacerbated by exposure to allergens and irritants, viral upper respiratory tract infections, bacterial sinusitis, exercise, and cold air. Nocturnal symptoms indicate more severe disease, causing awakening in the early morning hours (for those with a normal diurnal schedule). The clinical presentation of asthma is variable with respect to severity, underlying pathogenic mechanisms, effect on quality of life, and responsiveness to treatment.

Asthma may develop at any age, although onset is more frequent in childhood and young adulthood. Familial clustering occurs, suggesting that genetic factors are important. Risk factors for asthma include heredity, exposure to environmental tobacco smoke, viral infections in the first 3 years of life, and socioeconomic factors such as income level, the presence of cockroach or rodent infestations in the home, and access to medical care.12 Heritable factors include genes regulating IgE-related mechanisms, glucocorticoid response, airway smooth muscle development (ADAM33),15 and components of the immune system (HLA-G).16 Tobacco smoke is a common exacerbating factor in patients with asthma.

Physical findings in stable asthma are nonspecific, and physical examination findings can be normal when the patient is well. Poorly controlled asthma may exhibit auscultatory wheezing or rhonchi, but the intensity of wheezing is a poor indicator of the severity of either airflow obstruction or disease pathology. In an acute exacerbation of asthma, tachypnea, pulsus paradoxus (eg, a decrease of more than 10 mm Hg in systolic blood pressure during inspiration), cyanosis, and use of accessory muscles of respiration may be evident.

The term “exacerbation” may be used to indicate a short-lived worsening of symptoms managed effectively with short-acting β2 agents. It also may be used to indicate a more serious deterioration of lung function, of longer duration, associated with increased symptoms and commonly precipitated by exposure to allergens or viral infections, that may require intensification of anti-inflammatory therapy.

Atopic or allergic asthma is frequently associated with allergic rhinitis and conjunctivitis. Food allergies and atopic dermatitis may also be observed. Nonatopic asthma, defined as not associated with allergies, is less frequent than atopic asthma in patients with mild asthma (20%) or severe asthma (29%)17 and is more common in older adults compared with children; its evaluation and pharmacologic management are otherwise similar to that for atopic disease.

Adverse consequences of systemic steroid treatment may occur if frequent courses of systemic steroid therapy are necessary (Table 2). Allergic bronchopulmonary mycoses, including allergic bronchopulmonary aspergillosis, may have a prevalence as high as 25% among people with asthma, although the pathogenesis and causes of this complication remain uncertain.

In the setting of the above symptom complex and airway obstruction reversible by β2-agonists, the diagnosis of asthma can usually be made. A proposed algorithm for the diagnosis of asthma is presented in Figure 1. The combination of asthma-like symptoms and β2 agonist–reversible bronchial obstruction usually is sufficient to establish the diagnosis of asthma. Appropriate diagnostic testing should be conducted to confirm a diagnosis of asthma or suggest alternatives. Diseases of the heart and great vessels, the pulmonary parenchyma, and the upper airway can mimic the clinical presentation of asthma.

Variable Airway Obstruction
A cardinal feature of asthma is variable airway obstruction,32 a variation in airway caliber over the time frame of minutes to days; it is due to bronchoconstriction, mucosal inflammation, and luminal secretions, and results in increased airflow resistance and work of breathing. In more severe or longstanding disease, the airway obstruction may be entirely fixed or incompletely reversible with bronchodilator treatment. Bronchoconstriction occurs in airways that contain contractile airway smooth muscle. Enhanced parasympathetic cholinergic tone occurs in nocturnal asthma and can cause contraction of airway smooth muscle, increased mucus production, and increased airway obstruction.Factors associated with mucus overproduction and inflammation (allergen exposures, viral or bacterial infections)34 can also increase obstruction.

Airway Hyperresponsiveness
Airway hyperresponsiveness,32 an exaggerated reduction in airway caliber after a stimulus, has been recognized as a hallmark of asthma from the time of Claudius Galen, a physician in about ad 150. Although not specific, airway hyperresponsiveness is a virtually universal finding in asthma, and is associated with airway inflammation. Airway hyperresponsiveness may be induced by allergens (eg, pollen, animal danders),36 chlorine,37 pollutants (eg, sulfur dioxide),38 diesel exhaust particulates,36 and viral upper respiratory tract infections.39 Genetic variation accounts for some associations of environmental exposure and airway hyperresponsiveness,40 but specific genetic predispositions for airway hyperresponsiveness and other triggers remain poorly understood. Sympathetic control in the airway is mediated via β2-adrenoreceptors expressed on airway smooth muscle, which are responsible for the bronchodilator response to albuterol used in diagnosis and symptom relief and for longer-term bronchodilation facilitated by long-acting β2-agonist controller agents.42 (Short- and long-acting β2-agonists are used for distinct purposes in asthma therapy.) Cholinergic pathways may further contribute to airway hyperresponsiveness43 and are the basis for the efficacy of anticholinergic therapy23,44 The methacholine challenge test uses inhaled methacholine, a direct cholinergic agonist, to evoke concentration-dependent airway smooth muscle contraction.45 Bronchoconstriction at low concentrations of methacholine (typically <4 mg/mL) suggest increased airway hyperresponsiveness .

Airway Inflammation
Airway inflammation is recognized as a pathogenic factor in asthma.46 Inflammation involves many different cells (eosinophils, lymphocytes, mast cells, neutrophils) and is commonly initiated by allergen-dependent release of histamine and other mediators from mast cells47 and subsequent infiltration of lymphocytes (particularly T-helper type 2 [TH2]) and granulocytes into the airway.48 IgE occupies a central role in the pathogenesis of allergic asthma; inflammatory responses are mediated by allergen-specific IgE, generated during allergic sensitization, and bound to mast cells which are activated by reexposure to allergen. Elevated levels of proinflammatory cytokines IL-4, IL-5, and IL-13 are observed.49,50 Airway inflammation accentuates obstruction by promoting mucosal infiltration and edema, mucus secretion, and airway hyperresponsiveness; it also predisposes to exacerbations. Structural changes, termed airway remodeling, include increased smooth muscle mass,51 goblet cell hyperplasia,52 and lamina reticularis thickening.51 The TH2 hypothesis (activation of TH2 cells) provides conceptual understanding of the development of inflammation associated with asthma.53 More recently it has been recognized that type 2 innate lymphoid cells also contribute to eosinophilic airway inflammation. This phenomenon is termed “type 2 inflammation.”54 Eosinophilic inflammation and asthma may develop in the absence of overt allergy.55 Endogenous anti-inflammatory mediators appear to be important in controlling and resolving airway inflammation in individuals without asthma, and these mechanisms may be insufficiently or ineffectively activated in asthma: eg, reduced production of the anti-inflammatory factors IL-10 and lipoxin A4 has been identified in patients with asthma.

Activation of IL-17, CD4+ T cells (TH17 cells), and IL-12/IL-23 is distinct from type 2 factors noted above and is more closely associated with neutrophilic inflammation.58 Neutrophil infiltration and activation contribute to the severity of uncontrolled and severe asthma, and neutrophilic inflammation is less responsive to standard therapies, making the neutrophil an attractive potential target for novel asthma therapy.

Assessment and Diagnosis
The diagnosis and severity of asthma are established based on clinical criteria: history, physical examination, and evidence of either reversible airflow obstruction, or airway hyperresponsiveness (Figure 1).12,13 The US National Asthma Education and Prevention Program (NAEPP) approach to classifying asthma severity is based on 2 domains: impairment and risk. The impairment domain includes measured airway obstruction, the frequency and intensity of daytime and nocturnal symptoms, frequency of short-acting β2 agonist use for symptom relief, and interference of daily activities by symptoms. The risk domain assesses the frequency of exacerbations (Figure 2). These data collectively define both asthma severity and asthma control.12,13 Physical findings of accessory muscle use or audible wheezing during normal breathing may be present only during times of asthma exacerbation and have poor negative predictive value to exclude the diagnosis of asthma.

Spirometry is the most important diagnostic procedure for evaluating airway obstruction and its reversibility. It should be performed in all patients in whom asthma is a diagnostic consideration. The maximal volume of air forcibly exhaled from the point of maximal inhalation (forced vital capacity, FVC), the volume of air exhaled during the first second of this maneuver (FEV1), and FEV1:FVC ratio are 3 key measures. An FEV1:FVC ratio less than the lower limit of normal (0.7-0.8 in adults, depending on age) (Figure 2) indicates airway obstruction, although asthma may be present even without demonstrable airway obstruction (Figure 1). Reversibility of airway obstruction is indicated by an increase in FEV1 of 200 mL or greater and 12% or greater from baseline after inhalation of short-acting β2-agonists. In patients who have smoked cigarettes, distinguishing asthma with partially reversible obstruction from chronic obstructive pulmonary disease is challenging and has led to the description of an asthma–chronic obstructive pulmonary disease overlap syndrome, the existence and clinical importance of which is controversial.60 No validated approaches for differentiating these entities has been identified. A low diffusing capacity for carbon monoxide suggests an element of emphysema rather than asthma. Pulmonary function testing is less informative when performed during exacerbations of asthma and is best obtained during times of disease stability.

Bronchoprovocation with methacholine can be helpful in patients with suspected asthma and normal spirometry because a negative test result makes the diagnosis of asthma unlikely (Figure 1).61 Outside the United States, mannitol may be used as an effective bronchoprovocation agent.62 Methacholine and mannitol used as bronchoprovocation agents both have a sensitivity of approximately 80% and specificity of approximately 65%.

Impedance oscillometry, a technique that measures airway resistance without forced expiration, can measure central and peripheral airway resistance in those patients for whom the forced expiratory maneuver is difficult or impossible, including elderly patients.64 However, there is no consensus on the incremental value of impedance oscillometry over spirometry alone, nor are there sufficient data to establish the performance characteristics (sensitivity, specificity) of oscillometry vs spirometry alone in asthma.

In stable asthma, measurement of arterial blood gas values is rarely necessary, although it may be helpful in cases of acute decompensation and exacerbation. Periodic monitoring of pulse oximetry, with or without exercise, may be useful. Allergy evaluation has become increasingly important in recent years, as biologic agents have become available for treatment. A total serum IgE and specific IgE for common aeroallergens may be performed,12,13 as these tests can guide allergen avoidance strategies and suggest the potential use of anti-IgE monoclonal therapeutics. Allergy skin testing may be substituted for serum measures of allergen-specific IgE. A complete blood cell count with an elevated absolute eosinophil count can identify appropriate candidates for anti-IL-5 therapies (mepolizumab ≥150/µL and reslizumab ≥400/µL).

These diagnostic modalities are summarized in Table 3. The NAEPP12 presents a severity classification system based on historical features and spirometric measurements, and recently updated Global Initiative for Asthma (GINA) guidelines are also now available.13 Severity classes of intermittent, mild persistent, moderate persistent, and severe persistent asthma are defined, and severity categorization determines initial therapeutic approaches. The GINA guidelines also outline assessment of severity in patients already receiving effective controller therapy.

Asthma symptom control, using validated patient questionnaires (Asthma Control Test [ACT], Asthma Quality of Life Questionnaire [AQLQ], or Asthma Control Questionnaire [ACQ]) to provide a quantitative assessment of symptoms, may be assessed at each visit.12,65,66 (Because asthma symptoms and pulmonary function may not correlate well, measurement of both can inform adjustments to therapy.) Spirometry should be repeated every 1 to 2 years or with clinically significant change of asthma control to identify accelerated loss of lung function.12 Home peak flow monitoring may be useful in some patients for whom routine office spirometry cannot be performed. Patients with relatively normal pulmonary function test results, but persistent symptoms (eg, abnormal ACT, ACQ, or AQLQ scores) may be candidates for intensification of treatment. Persistently abnormal findings from pulmonary function tests suggest the need for intensification of the controller regimen. The utility of routine monitoring of the concentration of exhaled nitric oxide has not been established; however, patients who are not receiving adequate doses of inhaled steroids may show elevated concentrations (ie, >50 ppb) of exhaled nitric oxide.

There is little evidence to demonstrate the value of routine chest radiography in asthma. Chest imaging, beginning with a standard 2-view chest radiograph, may help to exclude other pulmonary pathology.12 Patients who are older than 65 years, have a clinically important history of smoking or significant occupational exposures such as mineral or organic dusts, have persistent symptoms despite therapy, or present with long-standing disease may be at risk for chronic obstructive pulmonary disease or lung cancer.

The optimal imaging modality has not been established; low-dose, high-resolution computed tomographic scanning provides considerably more information than a standard chest radiograph, but with increased radiation exposure and higher cost.

The goals of asthma treatment are reducing impairment (reducing symptoms, maintaining normal activities, achieving [nearly] normal pulmonary function test values) and minimizing risks associated with the disease (future exacerbations, medication adverse effects). Because of the heterogeneous nature of asthma and the limited availability of predictive biomarkers for treatment success, clinicians must approach patients with a guideline-based plan that recognizes specific environmental triggers and their mitigation (eg, allergens, viruses, or irritants encountered in occupational, household, or environmental settings), individual variability in the dose and particle size of inhaled corticosteroids, the class of long-acting bronchodilator (long-acting β2 agonist vs long-acting muscarinic antagonist), and other individual factors to provide an individualized treatment plan. A written asthma action plan that details in lay language the signs and symptoms indicating worsening of asthma, such as increased dyspnea or cough, or need for more frequent use of the β2 agonist inhaler, and the steps required to mitigate that worsening, is a key component of management.

Pharmacologic options are classified as either reliever (short-term benefit) or controller (longer-term benefit) medications (Table 2). All patients with asthma should have access to a short-acting β2 agonist inhaler (commonly albuterol) for treatment of acute symptoms; this intervention alone is appropriate for patients with intermittent asthma, defined as symptoms less than twice weekly with (near) normal pulmonary function. For patients with persistent asthma (defined as symptoms more than twice weekly or abnormal pulmonary function), a daily maintenance controller is generally appropriate. The initial choice of medication is directed by severity of asthma classification (intermittent; mild, moderate, or severe persistent [Figure 2]) at diagnosis. In the United States, guidelines recommend treatment based on 6 steps (Figure 3),12 but the GINA guidelines define 5 steps, which are not strictly comparable to the US guidelines.

In the US treatment guidelines, step 1 therapy is used for patients with intermittent asthma and consists of short-acting β2-agonists, administered as needed. (These agents are also used for quick symptom relief in all patients with asthma, irrespective of severity.) Step 2 therapy is indicated for mild persistent asthma and preferably consists of low-dose inhaled corticosteroids, which improve asthma outcomes such as lung function, symptoms, and exacerbations7,8,12,13 in a dose-dependent, but not necessarily dose-proportionate, manner (eg, a doubled dose of inhaled corticosteroids will not produce doubled improvement in lung function). The dose response to inhaled corticosteroids varies by the outcome measured (symptom reduction, lung function improvement, reduction in exacerbation).12 Inhaled corticosteroids reduce the infiltration and activation of eosinophils, TH2 cells, and other inflammatory cells. An oral leukotriene receptor antagonist may be as effective as inhaled corticosteroids and is an alternate first-line treatment.68 These agents block the action of cysteinyl leukotrienes, key mediators of airway smooth muscle contraction.

Patients with moderate persistent asthma should start at step 3 therapy with medium-dose inhaled corticosteroids or a combination of low-dose inhaled corticosteroids and a long-acting β2 agonist (Table 2). Longer-acting bronchodilators increase airway caliber for 12 to 24 hours. Spacers (large volume-holding chambers) may improve pulmonary delivery, reduce pharyngeal delivery, and reduce local adverse effects when used with compatible pressurized metered-dose inhaler systems, particularly for those patients for whom consistent coordination of inhalation with actuation of the device is a concern.

Patients diagnosed with severe persistent asthma, commonly characterized as near-continuous chest symptoms, the need for multiple inhalations daily of rescue β2 agonist, nightly awakenings from asthma symptoms, or FEV1 less than 60% predicted, should start at step 4, 5, or 6 and be referred for consultation with an asthma specialist (an allergist or pulmonologist).12,13 Medication options for these patients include medium- or high-dose inhaled corticosteroid plus long-acting β2 agonist combinations, inhaled long-acting muscarinic agonists (tiotropium),23 and biologic therapy.11- 13

Long-acting bronchodilators should never be prescribed without an accompanying inhaled corticosteroid. The US Food and Drug Administration–approved package insert of each long-acting β2 agonist contains a black box warning of the increased risk of adverse outcomes and death. However, recent prospective evidence suggests that long-acting β2-agonists, when used appropriately (ie, always in combination with inhaled corticosteroids), do not confer adverse safety consequences and in fact reduce the risk of exacerbations and adverse events in adults with moderate to severe asthma compared with inhaled corticosteroids alone.69

For suboptimally controlled asthma, a physician should search for common problems such as incorrect inhaler technique, poor adherence, exposure to allergens, exposure to personal or secondhand tobacco smoke, gastroesophageal reflux, sinusitis, or intercurrent viral infections. If control is not optimal, intensification of the therapeutic regimen is usually indicated. The precise timing of follow-up visits is a matter of clinical judgment, as no prospective trials exist that directly address this question. Follow-up may range from several days or weeks for patients with very poorly controlled or severe disease, to months for patients with well-controlled, milder, and stable asthma. Once asthma is well controlled for 2 to 3 months, treatment may be stepped down to the lowest dose of medication that adequately controls symptoms and lung function.12,13 Guidelines for deintensification of asthma therapy are not as well established as those for intensification, and there are no randomized clinical trials of step-down therapy on which to make specific recommendations.

For patients who continue to have uncontrolled asthma despite standard inhaled therapies, several parenteral biologic agents (monoclonal antibodies) are available. These agents act systemically by influencing the immunopathogenesis of asthma, rather than treating the consequences of inflammation and bronchospasm from within the airway, as standard controller therapies do (Figure 4). The central role of IgE in the pathogenesis of allergic airway disease makes IgE an attractive target for asthma therapy. Omalizumab is an anti-IgE monoclonal antibody used in allergic asthma accompanied by moderately elevated IgE level (30 to about 1000 IU/mL, depending on body weight) and evidence of sensitization to perennial aeroallergens. It reduces allergen-induced mast cell activation and decreases expression of IgE high-affinity receptors on mast cells70 (Figure 4). Omalizumab is given by subcutaneous injection every 2 to 4 weeks, at a dose and frequency determined by body weight and serum IgE levels, and is principally effective in reducing exacerbations and need for oral steroids.70 Retrospective analysis of omalizumab trials suggests that serum eosinophil counts in excess of 260/µL and fractional excretion of nitric oxide of at least 19.5 ppb may identify patients likely to improve with omalizumab. However, no biomarker has been subjected to rigorous prospective confirmation to determine its predictive value.70 Little improvement in pulmonary function is observed, so lung function testing is not a good monitoring tool to assess omalizumab response. Measurement of serum IgE levels after initiating treatment is not useful. The primary clinical outcomes by which response may be judged are asthma exacerbations and symptoms.

Interleukin 5 is centrally involved in the synthesis, maturation, homing, and activation of eosinophils, suggesting a role for anti-IL-5 in managing eosinophilic airway disease. Anti-IL-5 monoclonal antibodies (mepolizumab and reslizumab) have recently been approved in the United States for patients with severe asthma and peripheral eosinophilia.11 Mepolizumab reduces the rate of exacerbations by almost 50%; the need for oral corticosteroids is also reduced by 50%, with little effect on lung function.26,27 No specific level of peripheral blood eosinophilia is listed in the package insert, but the referenced clinical trials required at least 150 eosinophils/µL. This level of eosinophilia has not been prospectively assessed as a predictive biomarker of therapeutic response. Mepolizumab is administered by injection every 4 weeks, at a standard dose of 100 mg subcutaneously.

Reslizumab is administered every 4 weeks by intravenous infusion, using weight-based dosing (3 mg/kg). Reslizumab reduces the rate of exacerbations by about 50%, reduces symptoms, and improves FEV1 by 110 mL.28,29 Clinical trials referenced in the package insert required at least 400 eosinophils/µL for entry, but this requirement has not been validated as a predictive biomarker. Both mepolizumab and reslizumab reduce biologic activity of IL-5 in the pathogenesis of eosinophilic inflammation.

Oral steroids are an effective option for uncontrolled disease and for asthma exacerbations but have significant adverse effects, including glucose intolerance, weight gain, and salt and water retention, if used continuously .

Special Considerations
Consultation with an asthma specialist is warranted for patients who are at step 4 or higher in the US guideline13 or who have a life-threatening exacerbation, poor responsiveness to prescribed treatment, occupational triggers, atypical presentation, need for more than 2 bursts of oral corticosteroids, or who need specialized testing for allergies, lung function, or bronchoscopy.12,13 Asthma may present with symptoms predominantly in association with exercise. The timing of symptoms is generally within a few minutes of cessation of exercise and is termed “exercise induced bronchospasm.” Pretreatment with albuterol 15 minutes prior to anticipated exercise can minimize or eliminate these symptoms.12,13 Management of comorbid conditions (allergic rhinitis, sinusitis, gastroesophageal reflux, obstructive sleep apnea) improves asthma control.12,13 Adding exercise as a component of lifestyle change in overweight patients with asthma appears to improve asthma control.

Selected Current Controversies
All long-acting β2-agonists marketed in the United States carry a black box warning for increased risk of death and serious adverse events, based primarily on results from a large observational study with important limitations in study design. More recent evidence suggests that the appropriate use of long-acting β2-agonists in combination with inhaled steroids is not associated with increased serious adverse events.

Additional well-controlled studies may clarify this matter.

All biologic agents marketed in the United States require parenteral administration and are costly ($15 000-$30 000 annually). Omalizumab and reslizumab carry black box warnings for the risk of anaphylaxis, and their use is generally limited to asthma specialists. No data are available regarding direct comparisons of these agents, the optimal duration of therapy, or whether combinations of biologics are superior to individual treatments.

Bronchial thermoplasty, a procedure approved in 2010 for severe asthma, delivers radiofrequency energy to the airway. The mechanisms by which this procedure affects the pathogenesis of asthma remain unclear; changes in adaptive immunity and airway smooth muscle have been suggested but not proven.73 Reduced exacerbations (50%) and emergency department visits (85%) are seen for at least 1 year after treatment.74 Trials of up to 5 years were not rigorously controlled, so evidence for long-term benefit is limited.30 The GINA,13 but not the NAEPP,12 specify a role for bronchial thermoplasty. The American Thoracic Society and European Respiratory Society have recommended that bronchial thermoplasty be conducted within the context of a clinical trial or registry.75

Asthma continues to be an important cause of morbidity and some mortality in the United States (Table 1). Rates of asthma mortality are particularly elevated among non-Hispanic African American patients (25.4 per million per year) compared with white patients (8.8 per million per year).

Controller agents appear not to modify the natural history of asthma.12,13 Patients with persistent disease should be counseled that treatment for an extended period will likely be necessary. In patients with mild-moderate asthma whose disease is controlled with a daily regimen of low-medium dose of inhaled corticosteroids, the administration of these agents only at the time that short-acting β2-agonists are used for relief of symptoms provides control not different from that achieved with daily inhaled corticosteroids, using a reduced dose of inhaled corticosteroids; however, this approach has not yet been incorporated into formal guidelines.

Accelerated loss of lung function is seen in some, but not all, patients with asthma.77 Loss of lung function is principally observed in patients in whom exacerbations are frequent (2% predicted greater annual loss of FEV1 in patients with exacerbation compared with those without),78 highlighting the potential importance of preventing exacerbations. However, no long-term controlled trials having trajectory of lung function as the primary outcome have been published, so the effects of guideline-based treatment on loss of lung function remain unclear.


Asthma is characterized by variable airway obstruction, airway hyperresponsiveness, and airway inflammation. Management of persistent asthma requires avoidance of aggravating environmental factors, availability of short-acting β2-agonists for rapid relief of symptoms, and daily use of inhaled corticosteroids. Other controller medications, such as long-acting bronchodilators and biologics, may be required in moderate and severe asthma. Patients with severe asthma generally benefit from consultation with an asthma specialist for consideration of additional treatment, including injectable biologic agents.


Article Information
Corresponding Author: William J. Calhoun, MD, University of Texas Medical Branch, 4.116 JSA, 301 University Blvd, Galveston, TX 77555-0568 (

Diseñan una nueva pastilla para ayudar a los fumadores a dejar el # tabaco (Anticancer Res)

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Elimina el acetaldehído, un compuesto de los cigarrillos que desempeña un papel clave en la adicción al tabaco.

Elimina el acetaldehído, un compuesto de los cigarrillos que desempeña un papel clave en la adicción al tabaco.

Investigadores de la compañía finlandesa Biohit Oyj han desarrollado una nueva pastilla para dejar de fumar que contiene el aminoácido L-cisteína y que, según los últimos estudios publicados en la revista “Anticancer Research”, es segura y eficaz para abandonar el tabaquismo.

El aminoácido que contiene elimina el acetaldehído, un compuesto de los cigarrillos que se cree que desempeña un papel clave en la adicción al tabaco mediante la mejora de las respuestas del cerebro a la nicotina.

El equipo de investigación reclutó a cerca de 2.000 fumadores a los que dividió al azar en dos grupos. Mientras unos tuvieron que tomar una pastilla con cada cigarrillo durante seis meses, la otra mitad usaron en su lugar placebo.

Todos completaron un diario digital en el que tenían que precisar cuántos cigarrillos fumaban al día y el tiempo que dedicaban a cada uno.

En total, 753 personas siguieron todas las pautas que establecían los investigadores, mientras que 944 lo hicieron durante la mayor parte del tiempo.

A los seis meses, un total de 331 personas que terminaron el estudio habían dejado de fumar, 181 (18,2%) que tomaron la pastilla con L-cisteína y 150 (15%) que recibieron placebo.

Pero entre los que siguieron rigurosamente todas las instrucciones, 170 (45,3%) de los que usaron este compuesto han dejado de fumar, frente a los 134 (35,4%) del grupo control.

Los cambios en la sensación producida por el tabaco al fumar fueron motivo suficiente para dejar de fumar. Además, sólo un 6% de los fumadores presentaron algún tipo de efecto adverso, sin detallar cuáles.

El investigador Scott Sherman, del NYU Langone Medical Center de Nueva York (Estados Unidos), ha celebrado este “prometedor” avance pero admite que este fármaco aun no está listo para su comercialización indiscriminada, ya que su eficacia aún no ha sido comparada con otros tratamientos de deshabituación tabáquica.

Por su parte, la directora de la Augusta University’s Tobacco Control Initiative en Georgia, Martha Tingen, también ha observado ciertas limitaciones en el estudio, como el hecho de que un tercio de los voluntarios en el estudio no participó finalmente en él. Asimismo, tampoco se hicieron pruebas para constatar que los participantes dejaran realmente de fumar.

Add-On Azithromycin Associated with Fewer Asthma Exacerbations

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Azithromycin 3d structure.png
By Kelly Young

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM

Addition of azithromycin is associated with fewer asthma exacerbations in patients on dual maintenance therapy, according to a Lancet study.

Over 400 adults with symptomatic asthma who were using an inhaled corticosteroid plus a long-acting bronchodilator were randomized to receive oral azithromycin (500 mg) or placebo three times a week for 48 weeks. Patients with abnormal QTc prolongation or hearing impairment were excluded.

The azithromycin group experienced fewer moderate and severe asthma exacerbations than the placebo group (1.07 vs. 1.86 exacerbations per person-year). The treatment group also had better asthma-related quality of life, compared with placebo. However, azithromycin recipients were more likely to report diarrhea (34% vs. 19% of placebo recipients).

Azithromycin-resistant organisms, identified in sputum samples collected after treatment, did not differ significantly between the groups, but the authors note the study was not powered to detect an effect. Lancet commentators conclude: “The effects of long-term therapy with macrolides on community microbial resistance remain a public health concern.”


Lancet article (Free abstract)

Background: NEJM Journal Watch General Medicine coverage of study finding no effect on asthma with azithromycin use (Your NEJM Journal Watch registration required)

El aire acondicionado o los largos viajes en coche provocan un aumento de la sequedad ocular en verano

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En este periodo del año el ojo se encuentra sometido a un ambiente más hostil.

En este periodo del año el ojo se encuentra sometido a un ambiente más hostil.

Entre los meses de junio y septiembre existen varios factores que pueden repercutir negativamente en el bienestar de los ojos, como son la exposición al aire acondicionado o los largos viajes en coche, motivos por los que el ojo seco se posiciona como una de las dolencias más comunes en verano, pues “en este periodo del año el ojo se encuentra sometido a un ambiente más hostil”, según el director médico del Instituto Clínico-Quirúrgico de Oftalmología (ICQO) de Bilbao, el Dr. Durán de la Colina.

En este sentido, tal y como ha puntualizado el especialista del Departamento de Córnea y Superficie Ocular del Instituto de Microcirugía Ocular (IMO) de Barcelona, Óscar Gris, “el verano en sí, por la estación o la temperatura, no aumenta especialmente los casos de ojo seco; pero lo que sí es evidente es que son muchas las situaciones y los ambientes propios de estos meses que pueden producir más afecciones o agravarlas”.

Esta dolencia no solo empeora para aquellos que ya la padecían anteriormente, sino que, incluso, aquellas personas que no mostraban síntomas antes podrían empezar a hacerlo a partir, por ejemplo, de la capacidad que tienen los aires acondicionados a la hora de secar el ambiente y, por lo tanto, la superficie de los ojos, y “más aún cuando el aire da directo sobre la cara”, ha añadido el Dr. Durán de la Colina.

En cuanto a los viajes en coche, el Dr. Gris ha subrayado que “cuando se está conduciendo, se fija la vista para estar pendiente de la carretera y esto empeora mucho el ojo seco; lo mismo pasa cuando se hacen largos viajes en avión y se trata de distraerse con la lectura o los dispositivos móviles”.

Estas situaciones causantes de la sequedad ocular provocan que “se reduzcan las defensas del ojo ante los distintos estímulos irritativos propios de esta temporada, como son el cloro de las piscinas, la sal del mar o los fuertes rayos ultravioleta del sol, entre otros”, ha destacado el Dr. Durán de la Colina.

Sin embargo, no solo en verano existen factores que provoquen dicha sequedad, pues la calefacción en invierno, estar todo el día delante del ordenador en el trabajo, la televisión al llegar a casa o los múltiples dispositivos móviles que rodean la vida cotidiana, entre otros, requieren fijar la vista y parpadear menos, y esto, según el Dr. Gris, “hace que el ojo se acabe secando”.