Utility of long-read sequencing for All of Us.

The All of Us (AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compare the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis reveals substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also consider the advantages and challenges of using low coverage sequencing to increase sample numbers in large cohort analysis. Our results show that HiFi reads produce the most accurate results for both small and large variants. Further, we present a cloud-based pipeline to optimize SNV, indel and SV calling at scale for long-reads analysis. These results lead to widespread improvements across AoU.

Observing a dynamical skeleton of turbulence in Taylor-Couette flow experiments.

Recent work shows that recurrent solutions of the equations governing fluid flow play an important role in structuring the dynamics of turbulence. Here, an improved version of an earlier method (Krygier et al. 2021 J. Fluid. Mech. 923, A7 and Crowley et al. 2022 Proc. Natl Acad. Sci. USA 119, e2120665119) is used for detecting and analyzing intervals of time when turbulence 'shadows' (spatially and temporally mimics) recurrent solutions in both numerical simulations and laboratory experiments. We find that all the recurrent solutions shadowed in numerics are also shadowed in experiment, and the corresponding statistics of shadowing agree. Our results set the stage for experimentally grounded dynamical descriptions of turbulence in a variety of wall-bounded shear flows, enabling applications to forecasting and control. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical Transactions paper (part 1)'.

Managing asthma in adolescents and adults 2020 asthma guideline update From the National Asthma Education and Prevention Program

Asthma is a major public health problem worldwide and is associated with excess morbidity, mortality, and economic costs associated with lost productivity. The National Asthma Education and Prevention Program has released the 2020 Asthma Guideline Update with updated evidence-based recommendations for treatment of patients with asthma. To report updated recommendations for 6 topics for clinical management of adolescents and adults with asthma: (1) intermittent inhaled corticosteroids (ICSs); (2) add-on long-acting muscarinic antagonists; (3) fractional exhaled nitric oxide; (4) indoor allergen mitigation; (5) immunotherapy; and (6) bronchial thermoplasty. The National Heart, Lung, and Blood Advisory Council chose 6 topics to update the 2007 asthma guidelines based on results from a 2014 needs assessment. The Agency for Healthcare Research and Quality conducted systematic reviews of these 6 topics based on literature searches up to March-April 2017. Reviews were updated through October 2018 and used by an expert panel (n = 19) that included asthma content experts, primary care clinicians, dissemination and implementation experts, and health policy experts to develop 19 new recommendations using the GRADE method. The 17 recommendations for individuals aged 12 years or older are reported in this Special Communication. From 20 572 identified references, 475 were included in the 6 systematic reviews to form the evidence basis for these recommendations. Compared with the 2007 guideline, there was no recommended change in step 1 (intermittent asthma) therapy (as-needed short-acting ß2-agonists [SABAs] for rescue therapy). In step 2 (mild persistent asthma), either daily low-dose ICS plus as-needed SABA therapy or as-needed concomitant ICS and SABA therapy are recommended. Formoterol in combination with an ICS in a single inhaler (single maintenance and reliever therapy) is recommended as the preferred therapy for moderate persistent asthma in step 3 (low-dose ICS-formoterol therapy) and step 4 (medium-dose ICS-formoterol therapy) for both daily and as-needed therapy. A short-term increase in the ICS dose alone for worsening of asthma symptoms is not recommended. Add-on long-acting muscarinic antagonists are recommended in individuals whose asthma is not controlled by ICS-formoterol therapy for step 5 (moderate-severe persistent asthma). Fractional exhaled nitric oxide testing is recommended to assist in diagnosis and monitoring of symptoms, but not alone to diagnose or monitor asthma. Allergen mitigation is recommended only in individuals with exposure and relevant sensitivity or symptoms. When used, allergen mitigation should be allergen specific and include multiple allergen-specific mitigation strategies. Subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with symptoms and sensitization to specific allergens. Sublingual immunotherapy is not recommended specifically for asthma. Bronchial thermoplasty is not recommended as part of standard care; if used, it should be part of an ongoing research effort. Asthma is a common disease with substantial human and economic costs globally. Although there is no cure or established means of prevention, effective treatment is available. Use of the recommendations in the 2020 Asthma Guideline Update should improve the health of individuals with asthma.

Correlations between the leading Lyapunov vector and pattern defects for chaotic Rayleigh-Bénard convection.

We probe the effectiveness of using topological defects to characterize the leading Lyapunov vector for a high-dimensional chaotic convective flow field. This is accomplished using large-scale parallel numerical simulations of Rayleigh-Bénard convection for experimentally accessible conditions. We quantify the statistical correlations between the spatiotemporal dynamics of the leading Lyapunov vector and different measures of the flow field pattern's topology and dynamics. We use a range of pattern diagnostics to describe the flow field structures which includes many of the traditional diagnostics used to describe convection as well as some diagnostics tailored to capture the dynamics of the patterns. We use the ideas of precision and recall to build a statistical description of each pattern diagnostic's ability to describe the spatial variation of the leading Lyapunov vector. The precision of a diagnostic indicates the probability that it will locate a region where the Lyapunov vector is larger than a threshold value. The recall of a diagnostic indicates its ability to locate all of the possible spatial regions where the Lyapunov vector is above threshold. By varying the threshold used for the Lyapunov vector magnitude, we generate precision-recall curves which we use to quantify the complex relationship between the pattern diagnostics and the spatiotemporally varying magnitude of the leading Lyapunov vector. We find that pattern diagnostics which include information regarding the flow history outperform pattern diagnostics that do not. In particular, an emerging target defect has the highest precision of all of the pattern diagnostics we have explored.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

The Treatment of Allergic Respiratory Disease During Pregnancy.

Pregnancy may be complicated by new-onset or preexisting asthma and allergic rhinitis.This article reviews the recognition and management of asthma and allergic rhinitis during pregnancy, paying close attention to the general principles of allergy and use of asthma medication during pregnancy. Both allergic rhinitis and asthma can adversely affect both maternal quality of life and, in the case of maternal asthma, perinatal outcomes. Optimal management is thus important for both mother and baby. This article reviews the safety of asthma and allergy medications commonly used during pregnancy.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

The treatment of allergic respiratory disease during pregnancy

Pregnancy may be complicated by new-onset or preexisting asthma and allergic rhinitis. This article reviews the recognition and management f asthma and allergic rhinitis during pregnancy, paying close attention to the general principles of allergy and use of asthma medication during pregnancy. Both allergic rhinitis and asthma can adversely affect both maternal quality of life and, in the case of maternal asthma, perinatal outcomes. Optimal management is thus important for both mother and baby. This article reviews the safety of asthma and allergy medications commonly used during pregnancy (AU)

El embarazo puede complicarse por una nueva presentación de un asma y rinitis alérgica preexistentes. En este artículo se revisa el reconocimiento y manejo del asma y la rinitis alérgica durante el embarazo, con atención especial a los principios generales del tratamiento de la alergia y el asma durante esta situación. Ambas patologías pueden afectar de forma adversa a la calidad de vida de la madre y al periodo perinatal. El manejo óptimo de esta situación es muy importante tanto para la madre como para el hijo. Este artículo revisa la seguridad del tratamiento habitualmente utilizado durante el embarazo del asma bronquial (AU)

The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.

BACKGROUND: There is conflicting literature on the effect of maternal asthma on congenital malformations and neonatal outcomes. OBJECTIVES: This review and meta-analysis sought to determine if maternal asthma is associated with an increased risk of adverse neonatal outcomes. SEARCH STRATEGY: We searched electronic databases for: (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Cohort studies published between 1975 and March 2012 reporting at least one perinatal outcome of interest (congenital malformations, neonatal complications, perinatal mortality). DATA COLLECTION AND ANALYSIS: In all, 21 studies met inclusion criteria in pregnant women with and without asthma. Further analysis was conducted on 16 studies where asthmatic women were stratified by exacerbation history, corticosteroid use, bronchodilator use or asthma severity. MAIN RESULTS: Maternal asthma was associated with a significantly increased risk of congenital malformations (relative risk [RR] 1.11, 95% confidence interval [95% CI] 1.02-1.21, I(2)  = 59.5%), cleft lip with or without cleft palate (RR 1.30, 95% CI 1.01-1.68, I(2)  = 65.6%), neonatal death (RR 1.49, 95% CI 1.11-2.00, I(2)  = 0%), and neonatal hospitalisation (RR 1.50, 95% CI 1.03-2.20, I(2)  = 64.5%). There was no significant effect of asthma on major malformations (RR 1.31, 95% CI 0.57-3.02, I(2)  = 70.9%) or stillbirth (RR 1.06, 95% CI 0.9-1.25, I(2)  = 35%). Exacerbations and use of bronchodilators and inhaled corticosteroids were not associated with congenital malformation risk. AUTHORS' CONCLUSIONS: Despite limitations related to the observational nature of the primary studies, this review demonstrates a small increased risk of neonatal complications among pregnant women with asthma. Further investigations into mechanisms and potential preventive interventions to improve infant outcomes are required.

A meta-analysis of adverse perinatal outcomes in women with asthma.

BACKGROUND: Asthma is a common condition during pregnancy and may be associated with adverse perinatal outcomes. OBJECTIVE: This meta-analysis sought to establish if maternal asthma is associated with an increased risk of adverse perinatal outcomes, and to determine the size of these effects. SEARCH STRATEGY: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Cohort studies published between 1975 and March 2009 were considered for inclusion. Studies were included if they reported at least one perinatal outcome in pregnant women with and without asthma. DATA COLLECTION AND ANALYSIS: A total of 103 articles were identified, and of these 40 publications involving 1,637,180 subjects were included. Meta-analysis was conducted with subgroup analyses by study design and active asthma management. MAIN RESULTS: Maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22-1.75), small for gestational age (RR 1.22, 95% CI 1.14-1.31), preterm delivery (RR 1.41, 95% CI 1.22-1.61) and pre-eclampsia (RR 1.54, 95% CI 1.32-1.81). The relative risk of preterm delivery and preterm labour were reduced to non-significant levels by active asthma management (RR 1.07, 95% CI 0.91-1.26 for preterm delivery; RR 0.96, 95% CI 0.73-1.26 for preterm labour). AUTHOR'S CONCLUSIONS: Pregnant women with asthma are at increased risk of perinatal complications, including pre-eclampsia and outcomes that affect the baby's size and timing of birth. Active asthma management with a view to reducing the exacerbation rate may be clinically useful in reducing the risk of perinatal complications, particularly preterm delivery.

A survey of the burden of allergic rhinitis in the USA.

BACKGROUND: A prospective, cross-sectional, international survey was conducted among patients and physicians to identify symptom perception and the impact of allergic rhinitis (AR) on health-related quality of life (HRQoL). This paper presents the results from the USA. METHODS: Data were recorded by 447 patients and matched with data collected on these patients by primary care physicians or specialists. Tests to confirm a diagnosis of AR had been performed on 345 (77.2%) patients. Because of the intermittent nature of the disease, both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation, in addition to symptoms frequently, but not currently, present. Health-related quality of life was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: According to the physicians' assessment, a large proportion of patients had moderate or severe disease (62.6%; n = 280), persistent disease (47.0%; n = 213) and comorbidities such as asthma (28.4%; n = 127). Comparison of the physicians' and patients' assessment of disease severity found that patients rated their disease as more severe than physicians across all three types of AR (P < 0.001). At the time of the consultation, 44.0% (n = 197) of patients were suffering from nasal and ocular symptoms, and 23.7% (n = 106) of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. More than 50% of the patients surveyed (56.4%; n = 252) were using two or more medications for their AR. Health-related quality of life correlated negatively with the number of symptom-free days in the previous 4 weeks. Allergic rhinitis had a significantly greater impact on patients with more persistent disease compared with those with intermittent disease (2.3 +/- 1.3 vs 1.4 +/- 1.1; P < 0.001); nevertheless, approximately two-thirds of patients with intermittent disease reported some impairment of their professional or daily life as a result of AR. CONCLUSIONS: The results of this survey highlight the unmet needs of the many patients in the USA who present during routine care with moderate or severe and/or persistent disease and an associated high symptom burden and impaired HRQoL.

Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis.

Despite recent success in the treatment of early-stage disease, blastic phase (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge. The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression. To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays. Supervised microarray data analysis revealed 114 differentially expressed genes (P<10(-4)), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were downregulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-time-polymerase chain reaction and flow cytometry. Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy.

Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding.

Epitopes presented by major histocompatibility complex (MHC) class I molecules are selected by a multi-step process. Here we present the first computational prediction of this process based on in vitro experiments characterizing proteasomal cleavage, transport by the transporter associated with antigen processing (TAP) and MHC class I binding. Our novel prediction method for proteasomal cleavages outperforms existing methods when tested on in vitro cleavage data. The analysis of our predictions for a new dataset consisting of 390 endogenously processed MHC class I ligands from cells with known proteasome composition shows that the immunological advantage of switching from constitutive to immunoproteasomes is mainly to suppress the creation of peptides in the cytosol that TAP cannot transport. Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII).

Multilobated nuclei in Waldenström' macroglobulinaemia.

We report a case of Waldenström' macroglobulinaemia, where the bone marrow analysis showed an almost complete infiltration by a heterogeneous population, consisting of 80% small lymphoplasmacytoid cells and 20% large atypical cells with multilobulated nuclei. Both cell populations were CD19+ and CD38+ and contained IgM. Fluorescence in situ hybridization analysis with a chromosome 8 painting probe on interphase nuclei revealed only two signals in each cell, including in those with multiple nuclei. Our findings suggest that the multilobulated nuclear structures are diploid and originate from a single nucleus. In contrast to the published multiple myeloma cases, our patient showed good response to chemotherapy. After successful chemotherapy, the morphology of the lymphoma changed into typical lymphoplasmacytoid lymphoma. The multilobulated population was no longer detectable. Five years after the initial diagnosis, the patient is still alive and in good health.

Auer rod-like inclusions in multiple myeloma.

We report a case of IgA multiple myeloma, in which the plasma cells showed multiple azurophilic, Auer rod-like intracytoplasmic inclusions in May-Grünwald-Giemsa-stained marrow smears. Cytochemical stainings revealed a strong alpha-N-esterase activity of these inclusions, whereas the reactions for peroxidase, Sudan black, chloroacetate esterase, and PAS were negative. Immunostaining verified IgA-kappa inside the plasma cells. The inclusions, however, were negative. Amyloid and lysozyme were also not detectable. Electron microscopy showed Auer rod-like inclusions with a smooth surface in the neighborhood of a well-developed rough endoplasmic reticulum, but with no direct relation to it. The inclusions showed a fine lamellar substructure, and the periodicity of the filamentous striations was about 10 nm, comparable with the substructure of typical Auer rods. Our findings suggest that the azurophilic inclusions in multiple myeloma are Auer rod-related structures, which likewise consist of active lysosomal enzymes. In contrast to the Auer rods in acute myeloblastic leukemia (AML), however, the inclusions in multiple myeloma consist of typical plasma cell enzymes.

Regional chemotherapy of nonresectable colorectal liver metastases with mitoxantrone, 5-fluorouracil, folinic acid, and mitomycin C may prolong survival.

BACKGROUND: Regional chemotherapy of isolated, nonresectable colorectal liver metastases (CRLMs) by hepatic artery infusion (HAI) has the advantages of high response rates and the possibility of downstaging and resection of CRLMs. 5-Fluorodeoxyuridine (5-FUDR) has been the drug studied in most Phase II and III trials. The meta-analysis of the Phase III trials comparing HAI with systemic or supportive therapy confirmed an advantage for response and even survival for HAI. Hepatic artery infusion with 5-FUDR, however, is hepatotoxic, inducing sclerosing cholangitis (SC). The authors have introduced 5-fluorouracil (5-FU) with folinic acid for HAI and found equal effectivity but no SC when compared with HAI with 5-FUDR. Now, they report a new combination chemotherapy protocol based on HAI with 5-FU with FA and on in vitro Phase II studies suggesting mitoxantrone and mitomycin C as active drugs for HAI in CRLM. PATIENTS AND METHODS Between February 1993 and August 2000, 63 patients with CRLM were treated with HAI using mitoxantrone, 5-FU with FA, and mitomycin C (MFFM) via port catheters with a protocol planing up to 11 cycles of treatment. Toxicity and response were analyzed according to World Health Organization (WHO) criteria, and survival was analyzed according to Kaplan-Meier. All patients were treated with more than two HAI cycles. RESULTS: The objective response rate (complete remission and partial remission) was 54% and primary intrahepatic progression (progressive disease) occurred in 4.8%, whereas in 41.3% of the patients the intrahepatic disease was evaluated as no change. Median survival times from the first diagnosis of CRLM or start of HAI were 25.7 months and 23.7 months, respectively, and 7 patients lived longer than 40 months. Grade 3 toxicity according to WHO occurred in 34.9%, and Grade 4 occurred in 3.2%. No toxic death or SC occurred. CONCLUSIONS: Our new HAI protocol with MFFM seems to be superior to HAI with 5-FUDR, 5-FU with FA, and systemic chemotherapy with 5-FU and FA at acceptable toxicity. Currently, HAI with MFFM is compared with systemic chemotherapy using 5-FU and FA intravenously in a randomized Phase III trial.

Comparison of German language versions of the QWB-SA and SF-36 evaluating outcomes for patients with prostate disease.

BACKGROUND: The quality of well-being scale (QWB) and the Medical Outcome Study 36-item short form (SF-36) are alternative methods for measuring general health outcomes. Few studies compare these approaches against one another and no studies have compared German language versions. METHOD: A German language version of the self-administered quality of well-being scale (QWB-SA) was developed using forward and back translation methods. The German QWB-SA and a German language version of the SF-36 were administered to clinical population groups with current diagnoses of prostate cancer, benign hyperplasia of the prostate, colon cancer, and rectal cancer. Data were obtained from four German clinics. In addition to the quality of life measures, data on cancer stage and disease state were obtained. RESULTS: The QWB-SA and SF-36 were highly correlated. The QWB-SA was systematically related to disease state. Those with no symptomatic evidence had the highest scores followed by those who were stable with no metastatic disease and those with metastatic progression. Similar patterns were found for most SF-36 scales although the SF-36 failed to discriminate between those with no evidence of disease and those with stable disease without metastasis. CONCLUSIONS: Both the QWB-SA and SF-36 perform as expected using German language translations. Although both measures differentiate patients with metastasis from those without symptoms, the QWB-SA better differentiated those with no evidence of disease from those with stable disease without metastasis.

Developmental follow-up in 15-month-old infants of asthmatic vs. control mothers.

The purpose of this study was to evaluate mental and psychomotor development in infants of mothers whose asthma was actively managed during pregnancy and to compare the results with those froms infants of non-asthmatic mothers. Bayley Scales were assessed at age 15 +/- 3 months in 379 infants of asthmatic mothers and 376 control infants. Relationships were assessed between developmental indices and asthma severity, socioeconomic status, and infant prematurity. No significant differences in developmental indices were observed between infants of asthmatic mothers and control infants. No relationships were identified between developmental indices and maternal asthma severity. In the infants of both asthmatic and control mothers, a lower mean psychomotor developmental index was associated with birth weight < 2,500 g, and a lower mental developmental index with lower socioeconomic status. Hence, infants of asthmatic mothers whose asthma has been actively managed during pregnancy have developmental outcomes at 15 months of age that are similar to those of control infants.

The efficacy and safety of asthma medications during pregnancy.

Asthma may be the most common potentialy serious medical problem to complicate pregnancy. Because severe uncontrolled asthma may cause both maternal and fetal morbidity and mortality, pharmacological asthma therapy is often necessary during pregnancy. Only 1 published randomized controlled clinical trial has evaluated the efficacy of an asthma medication (inhaled beclomethasone) during pregnancy. Human data bearing on the safety of medications during pregnancy are usually limited to observational studies, because experimental studies on the use of medications during human pregnancy would generally be unethical. Existing observational cohort data do not associate an increased risk of preeclampsia, total congenital malformations, preterm birth, or low birth weight infants with maternal exposures to inhaled beta agonists, theophylline, cromolyn, or inhaled corticosteroids. Maternal use of oral corticosteroids has been associated with reduced birth weight, an increased risk of preeclampsia, and an increased risk of oral clefts (first trimester use). Based on this information, benefit-risk considerations suggest that inhaled asthma medications and theophylline should be used when indicated for the treatment of asthma during pregnancy. Moreover, although some increased risks may be associated with the gestational use of oral corticosteroids, these risks are probably still less than the potential risks to the mother and the fetus of severe uncontrolled asthma. This articles describes recently published consensus recommendations regarding the pharmacological management of asthma during pregnancy.