Asma Bronquial : Lactante y Preescolar

Asma Bronquial : Lactante y Preescolar
Causative factors for recurrent wheeze may vary from child to child and within a child over time, due to a large number of interactions between genetic factors and the environment [24 No existen marcadores de severidad pronósticos a largo plazo La mayoría de los pacientes inicia asma antes de los 6 años. Asma Bronquial : Lactante y Preescolar

Sibilancias / Asma Lactante y Preescolar
Dilema diagnóstico Naturaleza multifactorial de las sibilancias Descripción de Fenotipos / Confusos Dificultades en la evaluación funcional Desafío terapéutico. Deberían ser usados ………… The diagnosis of asthma in the very young is primarily difficult because of the lack of consistency of what is called asthma, and the failure to recognize the different phenotypes of asthma at different ages. Many classification and phenotypic descriptions have been proposed, but they continue to cause more confusion to already confused parents and perplexed physicians. Although these studies have provided much insight into the natural history of wheezy disorders, they have failed to affect clinical management to a large extent. Controversy persists as to when and why and how long inhaled corticosteroids (ICS) should be used in wheezy infants Dilema : Cúando usar cci ?? . Efectos adversos. No modifican la hria natural de la enfermedad Uso de cci en < de 5 años There are multiple non-asthma causes of wheeze, and there remains a lack of consensus in the description of wheezing phenotypes in this group of children. Childhood wheeze nevertheless presents a major burden of morbidity during preschool years, and there is significant progression from some childhood wheeze to adult asthma. More than 25% of an unselected birth cohort of children had wheezing that persisted from childhood into adulthood or that relapsed after remission.4 Comentar lo de guias británicas. Diagnosis of asthma in the under-fives is challenging due to the multiple non-asthma causes of early childhood wheeze and relies heavily upon clinical judgement since it is difficult to measure airflow obstruction in this age group. A recent consensus statement from the European Respiratory Society has discouraged the use of the term “asthma” in preschool children (<5 years) altogether.7 There is insufficient evidence showing that the pathophysiology of preschool wheezing illness is similar to that of asthma in older children and adults.10 little benefit is gained from investigations such as lung-function testing or bronchial challenge

Sibilancias : naturaleza multifactorial : Infecciones virales Inmadurez del sistema inmune Factores pre y post-natales ( tabaco ) Genes Epigenética Carácterísticas fisiológicas y anatómicas de un pulmón en desarrollo Sonnappa First, wheeze in preschool children is mostly associated with viral upper respiratory tract infections, which can recur frequently [9], and is usually not associated with any underlying airway inflammation, at least between episodes [10]. Second, while spon- taneous resolution of wheezing occurs in some of these children, in others wheeze can persist, and these children are at risk for developing asthma as conventionally defined in mid-childhood [1,11]. Cci deberían se usados …….. frequent exposure to viral infections; prenatal, perinatal, and postna- tal factors; genetic, epigenetic and environmental interactions; and, finally, unfavorable physiology and anatomy of the developing lung. La epigenética (del griego epi, en o sobre, y -genética) hace referencia, en un sentido amplio, al estudio de todos aquellos factores no genéticos que intervienen en la determinación de la ontogenia. Es la regulación heredable de la expresión génica sin cambio en la secuencia de nucleótidos. El término fue acuñado por C. H. Waddington en 1953 para referirse al estudio de las interacciones entre genes y ambiente que se producen en los organismos. La palabra “epigenética” literalmente signifi- ca “además de los cambios en la secuencia genética”. El término ha evolucionado para incluir cualquier proceso que altere la activi- dad del gen sin cambiar la secuencia del ADN, y conduce a modificaciones que pueden transmitirse a células hijas

Sibilancias : Frecuentemente Se asocia a IRAB viral Eur. Respir. J. 32, 1096–1110 (2008). No se asocia a inflamación subyacenre de la vía aérea. J. Allergy Clin. Immunol. 117(2 Suppl. 1), S216(2006). Evolución : Coexisten : sibilante transitorio / sibilantes persistentes N. Engl. J. Med. 332, 133–138 (1995). Am. J. Respir. Crit. Care Med. 172, 1253–1258 (2005). Sonnappa First, wheeze in preschool children is mostly associated with viral upper respiratory tract infections, which can recur frequently [9], and is usually not associated with any underlying airway inflammation, at least between episodes [10]. Second, while spon- taneous resolution of wheezing occurs in some of these children, in others wheeze can persist, and these children are at risk for developing asthma as conventionally defined in mid-childhood [1,11]. La hria continua : Unfortunately, the ability to predict who among these children will have transient versus persistent problems is poor.

≈ 50% de los preescolares tienen el antecedente de 1 episodio de sibilancias a los 6 años. N Engl J Med 1995;332:133-8. Solo 30% de los preescolares con SR tienen asma en edad de 6 años. J Allergy Clin Immunol 2003; 111: No existe un marcador específico ( genético y/o biomarcador ) Allergy 1999;54(suppl 49):24-8. < 3 años : peor control de su AB . J Allergy Clin Immunol 2003;111: Sonnappa : Wheezing in the preschool years is extremely common and it is estimated that approximately one in three children will have at least one episode of wheeze prior to their third birthday, and by 6 years of age this figure increases to almost 50% [1,2] API A Swiss study6 showed that children less than 3 years of age had significantly worse asthma control (more sleep disturbance, limitations in play and family activities, emergency department or general practitioner visits, and hospitalizations) compared with schoolchildren and adolescents. This article reviews the importance of determining at early ages which infants/preschoolers will have asthma later in life and proposes the use of the Asthma Predictive Index (API) to identify these children. Unfortunately, infants who wheeze and eventually have asthma coexist with a large group of infants with recurrent wheezing whose symptoms are transient and usually subside during early years of school. It is a challenge to distinguish between these groups during infancy and early childhood simply on the basis of clinical presentation. No accurate screening tests (using genetic or single biochemical markers) have been developed to determine which young children with recurrent wheezing will have asthma.7 Chronic inflammation is the most common feature of asthma, but measurements of inflammation are not yet a major factor in diag- nosing and monitoring asthma. Mencionar porque lo saqué Therefore the diagnosis and management of asthma in young children are primarily based on subjective clinical features and findings from medical examinations. Riesgo asma 2010 : Recurrent wheezing is a common problem, with approximately 50% of children experiencing wheeze in the first year of life,1 resulting in a substantial effect on the children, their families, and the health care system However, the diagnosis of persistent asthma remains imperfect, with only 40% of these infants experiencing continued wheezing symptoms in later childhood1 and with variation in expression of both symptoms and risk factors over time La hria continua : Therefore, at present, there are no diagnostic tools that can reliably predict the development of asthma among wheezy infants.

Fenotipos

Fenotipos Inicio y duración de la sibilancias ( Cohorte De Tucson )
Estado atópico Pattern de síntomas Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Pediatric Health (2010) 4(3), 267–275

Fenotipos Inicio y duración de la sibilancias Estado atópico
Pattern de síntomas Términos confusos Sobreposición de fenotipos Movilidad entre fenotipos Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Phenotypes are relevant only if the exercise can be justified in terms of under- standing the pathophysiology of the disease or it benefits the immediate treatment of the child [16]. Pediatric Health (2010) 4(3), 267–275

Fenotipo : Inicio y duración de los síntomas
child with wheeze can only be categorized into one of these three groups retro- spectively, hence usage is limited to epidemio- logical studies and not the clinical management of the child. CCI Deberían ser usados ……… In the last 2 decades, a wealth of epidemiologic studies, championed by the Tucson group, have been generated by retrospective analysis of large cohorts of wheezy infants,Department of Pediatrics, University of Louisville, Louisville, Kentucky.10INHALED STEROIDS USE IN INFANTILE WHEEZING11which have been followed prospectively.5,6 These studies described 3 patterns of wheezing based on presentation of symptoms. Early transient wheeze, nonatopic persistent wheeze, and atopic persistent wheeze. An important lesson from the Tucson Children’s Respiratory Study is that wheezy infants who develop asthma coexist with a larger group of infants with transient wheezing that disappear during preschool or school years, but distinguishing these 2 phenotypes, in the clinical setting, on the basis of their presentation can be problematic and unhelpful for the practicing clinician Lerr pdf 1 θ Leer fenotipos In the Tucson birth cohort, 34% of children wheezed during the first 3 yrs of life but 60% of these had ceased to wheeze by the age of 6 yrs. As a group, these infants with transient wheeze show reduced lung function prior to the first respiratory illness, are exposed to maternal smoking, and are not characterised by a personal history of eczema or a family history of asthma [1]. The 15% of children who started wheezing after the age of 3 yrs and were still wheezing at the age of 6 yrs were defined as having late-onset wheeze. This was associated with maternal asthma, male sex and a history of rhinitis [1]. This group tended to be atopic and show normal lung function at birth and through the teenage years [42]. Children who wheezed in the first 3 yrs and continued beyond the age of 6 yrs were termed persistent wheezers [1]. This was associated with normal lung function during the first year of life, but reduced lung function from the preschool age period and through adulthood (in most but not all cohort studies), with atopy and a family history of asthma [1, 4, 5]. De la cohorte de tucso : riesgo 2010 Children in the persistent wheezing (onset before age 3 years and still present at age 6 years) and late onset wheezing (symptoms after 3 years of age) groups, who are at increased risk of allergic sensitization, might represent those children who are most likely to experience asthma-like symptoms that persist into adolescence and adult life. Martinez. N Engl J Med 1995; 332:133-8 Pediatrics 2002;109;

Fenotipo : Inicio y duración de los síntomas. Transitorios
Prematuridad Tabaquismo durante el embarazo Tabaquismo pasivo Madre adolescente N Engl J Med 1995; 332:133-8 Pediatrics 2002;109; Lancet 348, 1060–1064 (1996) N Engl J Med 1995; 332:133-8 Allergol et Immunopathol 2008;36(5):280-90

Am J Respir Crit Care MedVol 172. pp 1253–1258, 2005

Fenotipo : Inicio y duración de los síntomas. Persistentes
N Engl J Med 1995; 332:133-8 Pediatrics 2002;109; Allergol et Immunopathol 2008;36(5):280-90

Persistente no atópico : 40% IRA baja por VRS Lancet 354, 541–545 (1999). PDF1 N Engl J Med 1995; 332:133-8 Pediatrics 2002;109; Allergol et Immunopathol 2008;36(5):280-90

N Engl J Med 1995; 332:133-8 Pediatrics 2002;109;

Fenotipo : según atopía
Persistente atópico 60% Deterioro de la función pulmonar / Asma Bronquial IgE total J. Allergy Clin. Immunol. 104,28–36 (1999). J. Allergy Clin. Immunol. 108, 709–714 (2001). Lancet 368, 763–770 (2006) J. Allergy Clin. Immunol. 111, 661–675 (2003).

Fenotipo : Inicio y duración de los síntomas. Tardios
Allergol et Immunopathol 2008;36(5):280-90

N:6.265 Sibilancias 6-18-30-42-54-69-81 m Evaluación : Fx P HRB TC
Asma y atopía clínica Estudio long de sibilancias A different approach was used by the British Avon Longitu- dinal Study of Parents and Children (ALSPAC) birth cohort, in which data on wheezing were available at 7 time points from birth to 7 years of age in 6,265 (45%) of the 14,062 unselected children recruited. Wheezy phenotypes were analyzed, applying a statis- tical analysis not limited by an a priori hypothesis about specific temporal phenotypes (latent class analysis).10 This largely confirmed the temporal wheezing patterns from the Tucson Child- ren’s Respiratory Study, as well as the associated risk factors. In addition, the analysis suggested a phenotype with ‘‘intermedi- ate-onset wheeze’’ (ie, onset of symptoms after 18 months of age) and another with ‘‘early prolonged wheeze’’ (ie, onset in the first year of life but remission at 69 months of age). Thorax 2008;63:974–980

Riesgo de Asma a los 91 meses
Precoz transitorio % Precoz Prolongado 36% Intermedio % Tardio % Persistente % Thorax 2008;63:974–980

Fenotipos : pattern de sibilancias
Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Fenotipos : pattern de sibilancias

The Task Force therefore realises that the phenotypes defined in the present report are not exhaustive, and that many individual patients may not fit into the categories described. There may be overlap between phenotypes and they may change over time. The purpose of the present Task Force was to produce guidelines for the treatment of wheezing in children aged ,6 yrs based on all of the available evidence. Asthma (GINA) guidelines, asthma is a syndrome with a highly variable clinical spectrum, characterised by airway inflammation [6]. Inflammation, however, has been poorly studied in preschool children, and may be absent in very young children who wheeze [14]. . Therefore, a symptoms-only descriptive approach, outlined in table 1, was adopted. The majority of the Task Force agreed not to use the term asthma to describe preschool wheezing illness since there is insufficient evidence showing that the pathophysiology of preschool wheezing illness is similar to that of asthma in older children and adults. Riesgo 2010 Young children might be difficult to place into accurate phenotypes given the change in risk factors over time. Thus, the persistent and late-onset wheezing phenotypes have also been described as multiple-trigger wheeze for children who wheeze when exposed to a variety of triggers rather than solely with viral infections to allow the clinician to better identify these children.3 Estudio long sibilancias Estudio fenotipos.These temporal patterns might reflect different endophenotypes, as demonstrated by differences in related risk factors. However, the clinical usefulness of such temporal phenotyping is limited by their retrospective definitions. CCI deberían ser usados …….. It was adopted by the European Respiratory Society (ERS) task force, which proposed that the terms transient, late-onset, and persistent wheeze should probably be limited to population-based cohort studies and should not be used clinically.11 They further proposed that wheeze should be described in terms of its temporal pattern and classified as episodic (viral) or multiple-trigger wheeze. For this reason, a different approach was selected to describe patterns and precipitants of symptoms: episodic wheezing is thought to be present only in association with viral upper respiratory tract infections; and multi-trigger wheezing, in which symptoms are present with and between viral infections. Uso de cci en < de 5 años A recent consensus statement from the European Respiratory Society has discouraged the use of the term “asthma” in preschool children (<5 years) altogether.7 There is insufficient evidence showing that the pathophysiology of preschool wheezing illness is similar to that of asthma in older children and adults.10 A simpler, two-phenotype, descriptive system for children <5 years has recently been proposed.7Episodic (viral) wheeze describes those children who wheeze in discrete episodes, commonly 2–4 weeks in duration, but are well between episodes. The trigger for such episodes is commonly viral upper respiratory tract infection. Multiple-trigger wheeze describes those who similarly wheeze during discrete episodes and have intermittent symptoms between episodes. Symptoms include nocturnal wheeze or cough and triggers may include cold air, exercise, laughing or crying

Sibilancias episódicas
Grupo más frecuente. Clin. Exp. Allergy 33, 573–578 (2003) N Engl J Med 1995; 332:133-8 Eur Respir J 2008; 32: 1096–1110 Factores de riesgo : prematuridad , exposición a tabaco , atopia. Duración variable Eur Respir J 2008; 32:1096–1110 Fenotipo variable Función pulmonar normal J. Allergy Clin. Immunol. (2010) Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] CCI deberían ser usados ………. In this model, episodic wheeze most commonly declines over time, disappearing by the age of 6 years, but can continue as episodic wheeze into school age, change into multiple-trigger wheeze or disappear at an older age.11 Episodic (viral) wheeze Episodic (viral) wheeze is defined as wheeze in discrete episodes, with the child being well between episodes. Although not unique to the preschool age group [26, 27], this phenotype appears to be most common in preschool children [1, 4, 5]. It is usually associated with clinical evidence of a viral respiratory tract infection, although microbiological diagnostic studies are rarely performed in clinical practice. The most common causative agents include rhinovirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, parainfluenza virus and adenovirus [28]. Repeated episodes tend to occur seasonally. . Factors underlying the frequency and severity of episodes are only partially understood, but the severity of the first episode (which is, in turn, related to pre-existent impaired lung function and younger age), atopy, prematurity and exposure to tobacco smoke have been implicated [29–35]. Episodic (viral) wheeze most commonly declines over time, disappearing by the age of 6 yrs, but can continue as episodic wheeze into school age, change into multiple-trigger wheeze or disappear at an older age [1, 26].

Sibilancias multigatilladas
Muchos gatillantes Mayor riesgo de desarrollar asma bronquial Duración variable Función pulmonar disminuida independiente del estado atópico Lancet 354, 541–545 (1999). J. Allergy Clin. Immunol. (2010) (In press) Eur. Respir. J. 32, 1096–1110 (2008). Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. Multiple-trigger wheeze Although a viral respiratory tract infection is the most common trigger factor for wheeze in preschool children, some young children also wheeze in response to other triggers (multiple- trigger wheeze; table 1). Others have used the term persistent wheeze for this syndrome, but this is confusing because this term is also used to describe the long-term temporal outcome of wheeze (discussed further later). Systematic studies of other such triggers are lacking. A textbook, written by two experts in the field, suggests that tobacco smoke and allergen exposure are important triggers, and that some children may also wheeze in response to mist, crying, laughter or exercise [23]. Although many believe that multiple-trigger wheeze in preschool children reflects chronic allergic airway inflammation (and could, therefore, be classified as asthma), there is little evidence to support this (see Investigations section). The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9]

Symptom-pattern phenotype and pulmonary function in preschool wheezers
Inert gas Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity (VI) is a non-invasive and safe lung function test that has been shown to be sensitive for detecting early pulmonary changes in CF.13e16 Several indices of ventilation inhomogeneity, such as the Lung Clearance Index (LCI) can be calculated from the washout curves describing presence and extent of VI. The LCI reflects overall VI within the peripheral and communicating zones of the lungs. Sibilancias y fxP sonnappa LCI was calculated by dividing the cumulative expired volume by the FRC, and Scond and Sacin were estimated by cal- culating phase III slopes, as previously described.22 Results: Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in Scond, and 15% (95% CI, 3% to 28%; P 5 .01) in sRaw compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P 5 .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), Scond was abnormal in 68% (95% CI, 61% to 74%), and sRaw was abnormal in 26% (95% CI, 16% to 35%) of multiple- trigger wheezers. Conclusions: Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. Scond is the most sensitive indicator of abnormal pulmonary function in preschool wheezers. (J Allergy Clin Immunol 2010;126: ) CCI deberían ser usados……… Sonnappa et al.12 recently showed that these 2 subsets of wheezy infants differ primarily in their lung function. Infants with multiple-trigger wheeze had lower lung function, with conductive airways ventilation inhomogeneity than infants with viral-triggered wheeze. Whether this finding indicates that the episodic/multiple-trigger classification does distinguish 2 functionally different phenotypes has been recently challenged.13 Whether this finding indicates that the episodic/multiple-trigger classification does distinguish 2 functionally different phenotypes has been recently challenged.13 It has been postulated that lower airway function may simply classify children according to disease severity, and not identify a differential disease mechanism, present before the symptoms occurred. In support of this contention are the results of another study14 suggesting that the proposed episodic/multiple trigger classification is not stable over time, and children frequently change from one type of clinically defined wheeze to the other even in the course of only 1 year. Indeed, in the course of 1 year, the stability of this phenotypic classification remained the same in only 45.9% of children and altered in 54.1% of children.14 Given these new challenging findings, the asthma predictive indices offer the advantage that they are quite stable over time and have been consistently shown to be acceptable predictors of subsequent development of persistent asthma symptoms.13 Indeed, in the course of 1 year, the stability of this phenotypic classification remained the same in only 45.9% of children and altered in 54.1% of children.14 Given these new challenging findings, the asthma predictive indices offer the advantage that they are quite stable over time and have been consistently shown to be acceptable predictors of subsequent development of persistent asthma symptoms.13 J Allergy Clin Immunol 2010;126:519-26

Problemas de la clasificación según Fenotipos
En la clasificación ERS : Evita el término de Asma Presentación variable. Las características clínicas de cada fenotipo tienen una modesta asociación. Carqcterísticas objetivas de cada fenotipo son costosas , difíciles de realizar, o plantean problemas éticos. Clinical & Experimental Allergy, 40, 1130–1141 Eur Respir J 2008; 32:585–92. J Allergy Clin Immunol 2010; 126:489–490. Acta Pædiatrica , pp. 56–60 E Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Uso de cci en < de 5 años Children may not fit clearly into either category, and there is neces- sarily overlap between these phenotypes which describe the extremes of a clinical spectrum in preschool children and reflect the multifactorial nature of wheeze. the classification does not allow for a prediction of the likelihood of subsequent development of “true asthma”; that is, persistent, atopic, multiple-trigger wheezing. It is the clinical progression from episodic to multiple-trigger, unremitting wheeze with atopic features such as dermatitis, aeroallergen sensitisation and impaired lung function that defines asthma—not the clinical presentation of early wheezing episodes.8 Las características clínicas de cada fenotipo cambia de uno a otro. con la edad y en cortos períodos. No uso de ERS : The recent work by Shultz et al. about thereliability of classifying preschool wheeze into episodic viral or multiple trigger contributes greatly to clear up the usefulness of such classification proposed by an ERS Task Force (1). The guidelines produced by that group avoided the use of the term asthma for preschool wheezers and defined the aforemen- tioned temporal patterns of wheeze to decide the suitable treatment (2). The observation that half of the children could evolve from one to other pattern in just 1 year discloses its inconsistence and answers the questions raised about the dangers of creating a flawed classification Clasificación ERS ?? The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze Phenotype as determined by retrospective parental report at the start of the study was not predictive of phenotype during the study year. Phenotypic classification remained the same in 45.9% of children and altered in 54.1% of children.

Factores de Riesgo

Factores de Riesgo / Sibilancias Persistentes
Sensibilización alérgica temprana . Marcha atópica Síntomas y diagnóstico de Asma Bronquial Disminución de función pulmonar Lancet 368, 763–770 (2006) J Allegy Clin Immunol. 1990;85:65-74. Immunol Allergy Clin North Am. 1998;18: Infecciones Virales Función Pulmonar Interacción Gen / Ambiente Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9]

Sensibilización alérgica temprana Diagnóstico de Asma Bronquial Disminución de función pulmonar Lancet 368, 763–770 (2006) Infecciones Virales Función Pulmonar Interacción Gen / Ambiente Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9]

Sensibilización alérgica temprana Diagnóstico de Asma Bronquial Disminución de función pulmonar Lancet 368, 763–770 (2006) Infecciones Virales Interacción Gen / Ambiente Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Respiratory viral infections are likely to play an important role in the development of wheeze and asthma Infection with respiratory syncytial virus in early life is an independent risk factor for wheeze (though not for atopic asthma), and the importance of rhinovirus is increasingly being recognised.16–19

The Arizona Children’s Respiratory Study
RISK OF WHEEZE AFTER RSV LRTI VS CONTROLS Frequent wheeze Infrequent wheeze *p ≤0.05 **p ≤0.01 ***p ≤0.001 5 *** 4 *** *** 3 ** Odds Ratios (95% CI) * 2 NS Clinical Evidence: Prospective Studies Two prospective studies have recently been conducted and reported. They differed in their design, but both found an association between RSV LRTI and subsequent RAD. Stein and associates followed a large outpatient cohort from the Tucson Children’s Respiratory Study. Findings: Significantly increased risk of frequent and infrequent wheeze by age 6 years among 207 children with mild RSV LRTI during infancy, compared with a reference group of children with no LRTI during the first 3 years of life (p≤0.001). Mild RSV LRTI was defined as not requiring hospitalization. The risk for frequent wheeze was still significantly increased at 11 years (p0.01). By age 13 years, there were no significant between-group differences. 1 6 years 8 years 11 years 13 years N= 207 children with mild RSV LRTI first 3 yrs not hospitalized Stein RT, et al. Lancet. 1999;354:541-5 Stein RT, et al. Lancet. 1999;354:541-5

Risk of Wheezing and/or Asthma
RSV LRTI: RISK FACTOR FOR ASTHMA & WHEEZING Risk of Wheezing and/or Asthma † * P = 0.003 ** P < 0.001 *** P < P <0.001 † * ** *** % of Group Sigurs and colleagues recruited 47 infants hospitalized with RSV bronchiolitis and concurrently recruited two matched control infants (in one instance, only one control was obtained), for a total of 93 controls. All the infants underwent follow-up evaluations at ages 1, 3, and 7 years. At 1 year, wheezing occurred in 40% of the RSV group compared with 16% of controls (p = 0.003), and physician-diagnosed asthma was present in 11% of the RSV group compared with none of the controls (p = 0.004).1 At 3 years, wheezing in the preceding year occurred in 40% of the RSV group, compared with 9% of controls (p < 0.001), and asthma was present in 23% of the RSV group and 1% of controls (p < 0.001).1 All 47 index and 93 control children were available for follow-up at 7 years.2 Any current wheezing occurred in 38% of the RSV group, compared with 2% of controls (p < ), and current asthma was present in 23% of the RSV group, compared with 2% of controls (p < 0.001). Note that at 7.5 years, cumulative prevalence of asthma was 30% in the RSV group, compared with only 3% in the control group. The results support the theory that RSV infection influences the mechanisms involved in the development of asthma. 1. Sigurs N et al. Pediatrics. 1995;95:500. 2. Sigurs N et al. Am J Respir Crit Care Med. 2000;161:1501. Sigurs et al. Am J Resp Crit Care Med. 2005; 171:137; Am J Crit Care Med. 2000; 161:1501 Pediatrics 1995;95:500

Wheezing Rhinovirus Illnesses in Early Life Predict Asthma Development in High-Risk Children
Rationale: Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood.Objectives: To define the relationship between specific viral illnesses and early childhood asthma development. Methods: A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase– polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed.Measurements and Main Results: Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age. Conclusions: Among outpatient viral wheezing illnesses in infancy and early childhood, those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort. Am J Respir Crit Care MedVol 178. pp 667–672, 2008

Indice Predictivo de Asma Bronquial
Sonnappa : However, wheeze phenotypes are not mutually exclusive and considerable overlap occurs, since phenotypes often relate to groups rather than individu- als [1,12–13]. Preschool wheezing in general represents complex interactions of many processes; there is often overlap between phenotypes and these phenotypes may change over time. The natural course of wheezing disorders in childhood is quite heterogeneous, and distinguishing between phenotypes is clinically important since etiology, pathophysiology, potential for therapy and outcome may differ [14]. However, there are a confusing number of terms used to describe preschool wheeze phenotypes owing to poor agreement on definitions, large overlap in phenotypes and because patients can move from one phenotype to the other [9] Indice Predictivo de Asma Bronquial

Indice Predictivo de Asma ( API )
Pdf1 API Upon applying this algorithm to the Tucson cohort, this produced a specificity of 97% (probability that the schoolchildren without asthma would have had a negative API in their infancy), a positive predictive value of 77% (probability of the infants with a positive API of having asthma at school age, or said differently, it was unable to detect 23% of persistent wheezers) and a negative predictive value of 69% (probability that the infants with negative API do not have asthma at school age, or that it was unable to detect around 30% of transient wheezers). The API was developed 10 years ago by using data from 1246 children in the Tucson Children’s Respiratory Study birth cohort. It was based on factors that were found during the first 3 years of life to predict continued wheezing at school age.15 A positive API score requires recurrent episodes of wheezing during the first 3 years of life and 1 of 2 major criteria (physician-diagnosed eczema or parental asthma) or 2 of 3 minor criteria (physician- diagnosis allergic rhinitis, wheezing without colds, or peripheral eosinophilia >_4%). A positive stringent API score by the age of 3 years was associated with a 77% chance of active asthma from ages 6 to 13 years; children with a negative API score at the age of 3 years had less than a 3% chance of having active asthma during their school years. For children who are ‘‘early wheezers during the first 3 years of life,’’ API negative predictive values ranged from 93.9% at 6 years of age to 86.5% at 13 years of age. For children who are ‘‘early frequent wheezers during the first 3 years of life,’’ the negative predictive values were 91.6% and 84.2% for 6 and 13 years of age, respectively Riesgo 2010 Active asthma was present in 76% of children with a positive API score, whereas asthma was not present in 95% of children with a negative score Sonnappa The API had a positive predictive value for active asthma of 47.5–51.5% between the ages of 6 and 13 years, and only 5% of children with a negative API had active asthma between the ages of 6 and 13 years [64]. The Prevention of Early Asthma in Kids (PEAK) trial modified the original API to include allergic sensitization to aeroallergens as a major risk factor and allergic sensitization to foods as a minor risk factor in place of physician-diagnosed allergic rhinitis [65]. Cci deberían ser usados ……… To help define the risk factors for asthma in later years, an asthma predictive index was developed after following almost a thousand children through 13 years of age.7 A stringent index requires frequent wheezing in the first 3 years of life plus 1 of 2 major criteria (atopic dermatitis in the child, parental diagnosis of asthma) or 2 of 3 minor criteria (diagnosis of allergic rhinitis in the child, eosinophilia [eosino- phils ‡4% of the total white blood cells], wheezing apart from colds). A loose index for the prediction of asthma requires any wheezing during the first 3 years of life plus 1 of 2 major criteria or 2 of 3 minor criteria.7 A positive stringent index was associated with asthma at school age in 76% of cases, whereas a negative stringent index was associated with an absence of asthma at school age in 97% of children. Uso de cci en < de 5 años Clinical indices such as the Asthma Predictive Index (API) have been developed based upon easily obtainable clinical parameters such as the presence of wheeze <3 years, parental history of asthma or eczema, eosinophilia, interval wheeze and allergic rhinitis.5 Their use is recommended for the early identification of serially wheezing patients at high risk of developing persistent asthma symptoms.6 There are concerns that such indices are insufficiently powerful to be of clinical value for individual patients.7 8 API positivo estricto : 76% probabilidad de AB en edad escolar. API negativo : 97% probabilidad de ausencia de AB en edad escolar J Allergy Clin Immunol 2010;126:212-6. Allergol et Immunopathol 2008;36(5):280-90

J. Allergy Clin. Immunol. 114, 1282–1287 (2004).
In an attempt to predict which preschool wheezers continue to wheeze beyond the age of 6 yrs, these history data have been combined with characteristics such as blood eosinophilia into an asthma predictive index [39]. Although groups of children with a positive asthma predictive index respond to inhaled corticosteroid (ICS) therapy [40, 41], the predictive value of this index for the disappearance or persistence of wheeze over time in individual patients is of only modest clinical value [39] A modified API (mAPI),24 which was tested in a randomized trial of 285 subjects, incorporated allergic sensitization to 1 or more aeroallergens as a major criterion and allergic sensitization to milk, eggs, or peanuts as a minor criterion, replacing physician-diagnosed allergic rhinitis from the original API CCI deberán ser usados …….. This index was further refined in 2004 to specify the frequency of wheezing as more than 3 exacerbations of wheezing in the past 12 months, with at least 1 physician-confirmed exacerbation. Additionally, this modified asthma predictive index includes allergic sensitization to ‡ 1 aeroallergen among the major criteria and re- places allergic rhinitis as a minor criterion with allergic sensitization to milk, egg, or peanuts.9 J. Allergy Clin. Immunol. 114, 1282–1287 (2004).

Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age
The Urban Environment and Childhood Asthma (URECA) study in Oslo developed a score (Oslo Severity Index) to assess if the severity of wheeze during the first 2 years of life predicts current asthma at 10 years of age [66]. The severity score was based on the following clinical criteria present from 0 to 2 years of age: number of episodes of wheeze, number of months with persistent wheeze and number of hospital admissions owing to wheeze, the maximum score being 12. A linear association was found for the severity score as a predictor for current asthma. Using a cut-off value above five gave a sensitivity of 52% and a specificity of 87%. Furthermore, children with severity scores above five had increased AHR compared with those with a severity score of zero [66]. La hria continua : Devulapalli et al. demonstrated that a high severity score of obstructive airways disease by 2 years of age is a strong risk factor for, and may predict, current asthma at 10 years of age [19] Un valor cut-off de 5 tuvo una sensibilidad de 52% y especificidad de 87% Thorax 2008;63:8–13. doi: /thx

Marcadores Inflamatorios

Marcadores Inflamatorios FeNO
Exhaled nitric oxide distinguishes between subgroups of preschool children with respiratory symptoms I : tos recurrente II : sibilancias + API no estricto III : sibilancias + API estricto J Allergy Clin Immunol 2008;121:705-9

Remodelación de la Vía Aérea

Early Detection of Airway Wall Remodeling and Eosinophilic Inflammation in Preschool Wheezers CCI deberçian ser usados….. Reticular basement membrane thickness was significantly higher, and eosinophilic inflammation was significantly greater in the wheezy infantsthanin ments).17thecontrolsubjects(P < 0.05fo Edad : años Am. J. Respir. Crit. Care Med. 176, 858–864 (2007).

Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction Edad promedio : 12 meses La hria continua : Bronchial biopsies obtained from infants with confirmed wheezing have shown increased thickness of the reticular basal membrane and significantly greater eosinophilic inflammation compared with samples from children with parent-reported wheezing or control subjects [59]. Am. J. Respir. Crit. Care Med. 171, 722–727 (2005).

Tratamiento/ Fenotipo
Considerar : Pattern de síntomas Estado atópico Indice Predictivo de asma Antecedentes de IRAB en etapas tempranas Score de severidad de las sibilancias Función pulmonar

Función Pulmonar Preescolar
Espirometría VEF1-VEF0.75-VEF0.5 Pletismografía corporal Técnica de oclusión Oscilometría de Impulso Reversibilidad a Broncodilatadores PEDIATRIC ALLERGY, IMMUNOLOGY, AND PULMONOLOGY Volume 24, Number 1, 2011 CCI deberían se usados….. Wheezy infants constitute a heterogeneous group of patients. A complex and detailed work-up is usually necessary to arrive at the correct diagnosis. Prescribing therapy tar- geted at the cause of wheezing is the most common approach in managing these patients. A simple approach would be first to exclude other diagnoses based on ‘‘warning flags,’’ that is, symptoms of cystic fibrosis, reflux, aspiration, and underlying diseases such as severe neurodevelopment handicap, and then a therapeutic trial of asthma treatment, such as bronchodilators, ICS, and MK. When wheezy symptoms are refractory to conventional asthma therapy, then judicious use of diagnostic tests and individualized approach are required. An accurate diagnosis depends on a detailed medical history that includes possible risk factors for developing asthma, and a temporal description of the wheezing, a thorough physical examination, and an under- standing of the numerous differential diagnoses. Investiga- tions for the wheezy infants are justified when symptoms are present from birth, and or the airway obstruction is abnor- mally severe, the recovery is very slow or incomplete resulting in prolonged or repeated hospital admission in the first few years of life, and the wheezy episodes continue in the absence of viral infections.11 A provocative, somewhat invasive study based on a fixed protocol of investigations including a chest computed tomography scan, blood tests, nasal ciliary brushings, fiberoptic bronchoscopy, bronch- oalveolar lavage, endobronchial biopsy, and passage of an oesophageal pH probe found that infants and young children with severe recurrent wheeze, who remain symptomatic despite a trial of inhaled steroids, yield positive diagnosis in three-quarters of cases.4 Of these, 39% were atopic, two-thirds had evidence of gastro-oesophageal reflux, and 37 out of 47 had an abnormal bronchoscopy.4 We have proposed an individualized diagnostic approach to the causes of infantile wheezing29,30 based on infant pulmonary function testing. We found a positive response to bronchodilators to be a distinguishing variable in wheezy infants with peripheral airway obstruction Risk factors should not be overlooked, and all infants with wheezing should not be treated in similar fashion, but treatment plans should be based on the underlying cause of wheezing J Allergy Clin Immunol 2005;115:657-66

Tratamiento / Recomendaciones
API estricto positivo Corticoides Inhalados en dosis bajas Am J Respir Crit Care Med 2005; 171:587–590. N Engl J Med 2006; 354:1985–1997. Severidad de las sibilancias National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Be- thesda: National Heart, Lung and Blood Institute, 2007. CCI deberían ser usados en……. Low dose ICS are now recommended as the preferred initial treatment for infants and children who have > 3 episodes of wheezing per year lasting more than 1 day, and the presence of a major factor such as parental history of asthma or eczema, or 2 minor factors, such as eosinophilia, wheezing without colds, or allergic rhinitis. Studies have shown that when preschool children with wheeze are selected on the basis of the asthma predictive index, they seem to respond to ICSs as a group.22,23 reatment is also recommended for infants requiring symptomatic treatment with a short acting beta agonist for more than twice weekly, and or the occurrence of severe exacerbations <6 weeks apart.8 This new algorithm also judiciously suggested that if no clear benefit is observed in 4 to 6 weeks, to consider adjusting therapy or alternative diagnoses, meaning that not all wheeze is asthma Similarly, the ERS task force suggests ICS as an initial therapy for multiple triggers wheeze, and montelukast (MK) for episodic wheeze, but due to the overlap of phenotypes the ERS recommend that ICS and MK can be used on a trial basis in any situation, but should be discontinued if no clear benefit is obtained.11

Tratamiento / Recomendaciones
Recomendaciones de ERS Sibilancias Multigatilladas Corticoides Inhalados Sibilancias Episódicas Antileucotrienos Ensayo Terapéutico ( Sobreposición de fenotipos ) Corticoides Inhalados o Antileucotrienos CCI deberían ser usados en……. Low dose ICS are now recommended as the preferred initial treatment for infants and children who have > 3 episodes of wheezing per year lasting more than 1 day, and the presence of a major factor such as parental history of asthma or eczema, or 2 minor factors, such as eosinophilia, wheezing without colds, or allergic rhinitis. Studies have shown that when preschool children with wheeze are selected on the basis of the asthma predictive index, they seem to respond to ICSs as a group.22,23 reatment is also recommended for infants requiring symptomatic treatment with a short acting beta agonist for more than twice weekly, and or the occurrence of severe exacerbations <6 weeks apart.8 This new algorithm also judiciously suggested that if no clear benefit is observed in 4 to 6 weeks, to consider adjusting therapy or alternative diagnoses, meaning that not all wheeze is asthma Similarly, the ERS task force suggests ICS as an initial therapy for multiple triggers wheeze, and montelukast (MK) for episodic wheeze, but due to the overlap of phenotypes the ERS recommend that ICS and MK can be used on a trial basis in any situation, but should be discontinued if no clear benefit is obtained.11 Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefitJanuary Accepted after revision: May Maintenance treatment of multiple-trigger wheeze 1) ICSs at a daily dose of up to 400 mg?day-1 beclometasone equivalent should be given for the treatment of preschool children with multiple-trigger wheeze. 2) When the response to this treatment is poor, patients should not be treated with higher doses but should probably be referred to a specialist for further evaluation and investigations. 3) If response to inhaled steroids is favourable, treatment should probably be discontinued after several weeks or months, in order to judge whether symptoms have resolved or whether ongoing treatment is needed. 4) Linear growth should be measured in preschool children using ICSs. 5) Infants younger than 1 yr should probably not be prescribed ICSs. 6) Infants aged 1–2 yrs should only be prescribed ICSs if their symptoms are troublesome and they show a clear-cut response to treatment. 7) A trial of montelukast may be considered in preschool children with multiple-trigger wheeze. 8) Cromones, ketotifen and xanthines are not recommended for use in preschool children with wheeze. 9) Immunotherapy is not recommended for preschool children with wheeze outside the setting of a randomised controlled trial. 10) Influenza immunisation is not recommended for preschool children with wheeze. Uso de cci en < de 5 años Montelukast is recommended at the start of an episode of viral-induced wheeze while regular maintenance ICS are of benefit for multiple-trigger wheeze.7 Overlap and clinical evolution between episodic and multiple- trigger wheeze mean it is reasonable to attempt a trial of montelukast and ICS in any preschool child with recurrent wheeze. Therapy should be subsequently modified on the basis of clinical benefit. No validated tool exists for children <4 years, although working guidelines based upon frequency of symptoms, exercise limitation and need for reliever therapy have been developed for use in the under-fives.11 La hria continua ; Maintenance treatment with ICS in episodic viral wheeze in low-to-medium dosage seems not beneficial. Intermittent treatment with high-dose ICS during wheezing episodes has some beneficial effects but increases the risk of systemic side effects. An alternative possibility for this phenotype is treatment with montelukast, which reduced the rate of wheezing episodes in 549 preschool children with episodic viral wheeze by 32% compared to placebo [12]. Children with multiple-trigger wheeze often develop symptoms after crying, laughter or exercise. Based on these findings, many believe that multiple-trigger wheeze resembles allergic asthma, but there is little direct evidence to support this. It remains unknown whether the histopathol- ogy of the airways from children with multiple-trigger wheeze resembles that of allergic asthma. However, a proportion of preschoolers with persistent wheeze do develop asthma in later life [49,78] There is solid evidence that maintenance treatment with a low-to moderate dose of ICS decreases the number of days with asthma symptoms in children with multiple- trigger wheeze. However, Kaditis et al. [37] questioned whether the relative benefit of continuous treatment with ICS (approximately 5% fewer symptom-free days versus placebo) is clinically significant and outweighs the possible side effects. Montelukast improved symptoms and achieved a 30% reduction in exacerbations in 689 preschool children with multiple-trigger wheeze [41], but head-to-head com- parisons with an inhaled corticosteroid are not available in the literature [7,13] (Table 1). Eur J Pediatr (2011) 170:709–718 Eur Respir J 2008; 32:585–92

Tratamiento Mejoran calidad de vida pero no alteran la evolución natural de la enfermedad Reducción de la velocidad de crecimiento durante su uso Pediatrics 2009; 123:e519–e525. N Engl J Med 2006; 354:1985– 1997. CCI deberían ser usados en……. Low dose ICS are now recommended as the preferred initial treatment for infants and children who have > 3 episodes of wheezing per year lasting more than 1 day, and the presence of a major factor such as parental history of asthma or eczema, or 2 minor factors, such as eosinophilia, wheezing without colds, or allergic rhinitis. Studies have shown that when preschool children with wheeze are selected on the basis of the asthma predictive index, they seem to respond to ICSs as a group.22,23 reatment is also recommended for infants requiring symptomatic treatment with a short acting beta agonist for more than twice weekly, and or the occurrence of severe exacerbations <6 weeks apart.8 This new algorithm also judiciously suggested that if no clear benefit is observed in 4 to 6 weeks, to consider adjusting therapy or alternative diagnoses, meaning that not all wheeze is asthma Similarly, the ERS task force suggests ICS as an initial therapy for multiple triggers wheeze, and montelukast (MK) for episodic wheeze, but due to the overlap of phenotypes the ERS recommend that ICS and MK can be used on a trial basis in any situation, but should be discontinued if no clear benefit is obtained.11 In a recent meta-analysis on the efficacy of ICS in preschoolers with recurrent wheezing or asthma for at least 6 months before study entry, spanning many years and including thousands of subjects, Castro-Rodriguez et al.24 found that patients who received ICS had significantly less wheezing/asthma exacerbations than those on placebo (18.0% versus 32.1%). Further, positive response to ICS was higher in those with a diagnosis of asthma than wheeze but was independent of age (infants versus preschoolers) and the atopic condition. In addition, children treated with ICS had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less albuterol use, and more clinical and functional improvement than those on placebo.24 Other potential roles for ICS in addition to achieving symptoms control are to reduce disease severity. Indeed, in preschool children with intermittent moderate to severe wheezing and a positive modified asthma predictive index, continuous use of ICSs for 2 years led to significant im- provements in disease burden, including reduction in symptoms and diminished oral corticosteroid use.23 This was accompanied, however, by a statistically significant but transient reduction in linear growth velocity.23 Despite the fact that ICS seems to improve control of symptoms, they have not been capable to prevent the decline in lung function and the development of irreversible obstruction and airway remodeling. The study by GuilbertINHALED STEROIDS USE IN INFANTILE WHEEZING13et al.23 provides contrasting evidence that treatment with ICS in early life does not alter the natural history of asthma as effects did not carry over after the drug was stopped during the third study year. It is unknown whether continuous use of the same ICS would have had any substantial benefit on airway remodeling, or perhaps the use of an ICS that can penetrate deep into the small airways, a site of significant inflammation in asthma, could have resulted in a different outcome. Nonetheless, equally important were the com- ments by Gold and Fuhlbrigge, on this study that in recog- nition of the fact that the diagnosis of asthma is difficult in the very young, a diagnostic trial of inhaled bronchodilators and anti-inflammatory medications may be helpful, with careful monitoring of the response to therapy.28 Uso de cci en < de 5 años Despite initial enthusiasm for ICS, it is now well established that no disease-modifying therapy for wheezing in preschool children exists. Two- year ICS treatment of <4-year-olds with a positive API resulted in no subsequent disease-modifying impact after discontinuation of therapy.22 Therefore, treatment of this age group is aimed at the relief of symptoms to allow the child to lead as normal a life as possible with as little medication and disruption of family life as possible. Regular, maintenance ICS in multiple-trigger wheeze result in improved symptoms, exacerbation rates and lung function, but the use of intermittent ICS is more controversial.23 La hria continua : Recent early intervention studies with ICS in young children aimed at the prevention of asthma have shown no beneficial results with respect to the development of asthma [11,29,52], and the results of therapeutic studies are conflicting. Kaditis et al. [37] and Castro-Rodriguez et al. [17] reviewed the literature on the efficacy of ICS in recurrent wheezing preschool children. Based on these systematic reviews, as well as a number of randomised, double-blind, placebo-controlled clinical trials published after this review was completed, it is concluded that continuous treatment with ICS decreases the number of days with symptoms among children with persistent wheezing, without prevent- ing the need for hospitalisation [14] and had less wheezing/ asthma exacerbations and improved their symptoms and lung function, respectively [17].

Conclusiones Lactante / Preescolar
“ No todo lo que sibila es Asma “ Diagnóstico : Descartar otras enfermedades Diagnóstico : Buena respuesta a tratamiento Objetivo Mejorar calidad de vida Elección del tratamiento Considerar todas las herramientas Tratamiento individualizado Elección del tipo de droga según respuesta a tratamiento No uso de ERS Diagnosis of childhood asthma depends on the presence of a syndrome (wheezing or bronchial episodes), on the absence of other diseases, and on the response to asthma treatments. Wheezing is only a symptom,notadisease Classifying childhood asthma is of no proven help to choose the best treatment for a single patient. The response to anti- inflammatory drugs (inhaled steroids or montelukast) is not predictable on the basis of the information available in clinical practice. We are compelled to follow a trial-and-error strategy in search of the best treatment for the patient (4). Individual or social factors may induce to try first with one or the other drug, but it is only the response of the patient what decides the right choice. Acta Pædiatrica , pp. 1114–1116

Asma Bronquial : Lactante y Preescolar

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Asma Bronquial : Lactante y Preescolar

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